CN108822015A - The synthetic method of beta carotene - Google Patents
The synthetic method of beta carotene Download PDFInfo
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- CN108822015A CN108822015A CN201810818995.0A CN201810818995A CN108822015A CN 108822015 A CN108822015 A CN 108822015A CN 201810818995 A CN201810818995 A CN 201810818995A CN 108822015 A CN108822015 A CN 108822015A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07C403/24—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 six-membered non-aromatic rings, e.g. beta-carotene
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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 System
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Abstract
Organic phosphonium salt is prepared by retinol or derivatives thereof in the synthetic method of beta carotene, in the presence of vfanadium compound catalyst and molecular sieve, in oxygen atmosphere, intermolecular oxidative coupling reaction occurs, obtains beta carotene.Using clean and environmental protection, economical and easily available, Portable safety oxygen-containing gas as oxidant, it is safe from harm to environment, it is at low cost, it is conducive to industrialized production.Catalyst is done using vfanadium compound, significantly reduces the coupling reaction time；Co-catalyst is done using molecular sieve, reduces catalyst usage amount, improves catalytic oxidation effect, reduces the discharge of metal ion waste water.Polyethers phase transfer catalyst, which is added, can cause the reaction in heterogeneous reaction system between substrate；The formed complex compound of solid-state alkali compounds and be dissolved in organic phase and participate in reaction, effectively control the solubility of alkali in organic phase, inhibit the generation of by-product while promoting reaction to carry out, increase the yield of kind of product, to achieve the purpose that improve yield.
Description
Technical field
The present invention relates to beta carotenes, more particularly, to the synthetic method of beta carotene.
Background technique
Beta carotene is vitamin a source substance, can be used for medicine, food, cosmetics, feed addictive, dye industry,
It has good market prospects.
The country is many about the research report that beta carotene synthesizes, can be by beta carotene according to the difference of reaction route
Synthetic route be divided into C19+C2+C19, C15+C10+C15 and C20+C20 condensation reaction.Wherein by retinol or its derivative
Organic phosphonium salt that object is reacted with triphenylphosphine is the important intermediate of beta carotene, he can be with further occurrence C20+
C20Wittig condensation reaction prepares beta carotene, and oxidative coupling is anti-between self-molecules present can also occurring in the presence of oxidant
Beta carotene should be prepared；
Wittig condensation reaction route：Organic phosphonium salt that retinol or derivatives thereof is obtained with three aromatic radical phosphine reactions,
Organic phosphonium salt, which is further reacted with axerophthal by Wittig, is condensed to yield beta carotene.Wittig reacts in the technique
It is required that anhydrous and oxygen-free, condition is harsh, and axerophthal unstable chemcial property, is not easy industrially prepared.Reaction equation is as follows：
Oxidative coupling reaction is that oxidative coupling obtains beta carotene between the VA phosphonium salt of two molecules.Due to beta carotene
Symmetrical configuration, thus between the organic phosphonium salt of two molecules carry out oxidative coupling reaction prepare beta carotene process route it is more simple
It is clean.Reaction equation is as follows：
Beta carotene is prepared in the prior art by oxidative coupling reaction, and Chinese patent CN101081829A, which is disclosed, to be made
Coupling reaction is carried out in the presence of an oxidizer with organic phosphonium salt of retinol or derivatives thereof and obtains beta carotene, is used
Oxidant is hypochlorite, chlorate, hydrogen peroxide, SODIUM PERCARBONATE, oxygen or air；The substance is in water phase and organic solvent structure
At two-phase system in react, since in reaction process, organic phosphonium salt can be undergoneDynamic it is flat
The right end of weighing apparatus, the dynamic equilibrium is phosphonium ylide, and phosphorus ylide is very sensitive to protonic solvents such as water, meets water or easy point of heating
Solution.So carrying out above-mentioned oxidative coupling reaction in Aquo System, because of the unstability of intermediate, target product yield is not high.
Oxygen is a kind of generally acknowledged Green Oxidant, and reaction product is water, has many advantages, such as economical and practical environmental protection, existing skill
Art once reported the application carried out in relation to oxygen in the organic phosphonium salt of vitamin A in oxidative coupling reaction, but according to existing result of study
Showing molecular oxygen, in above-mentioned coupling reaction, not only reaction rate is slow as oxidant, and product yield is low, sometimes or even does not react.
Summary of the invention
In view of the above-mentioned deficiency of the prior art, the purpose of the present invention is to provide easy to operate, reaction condition is mild, cost
It is low, yield is higher, suitable for industrialized production beta carotene preparation method.
The specific steps of the present invention are as follows：
Organic phosphonium salt is prepared by retinol or derivatives thereof, in the presence of vfanadium compound catalyst and molecular sieve,
In oxygen atmosphere, intermolecular oxidative coupling reaction occurs, obtains beta carotene.
The solid-liquid two that the intermolecular oxidative coupling reaction is constituted in organic solvent, phase transfer catalyst and alkali compounds
It is carried out in phase reaction system, reaction route is as follows：
Wherein, R1, R2, R3 are aromatic group, aliphatic, alicyclic group, described R1, R2, R3 be phenyl, benzyl,
Cyclohexyl or butyl；It is described for the acid group of inorganic acid or the acid group of organic acidCan be selected from bisulfate ion, sulfate radical,
One of tetrafluoroborate, phosphate radical, acetate, tosylate, benzene sulfonic acid root etc., preferably chloride ion, bromide ion or iodine
Ion etc..
Organic phosphonium salt, which reacts under the action of phase transfer catalyst with alkali compounds, generates phosphonium ylide, in part
Mesosome ylide is oxidized to corresponding VA aldehyde under the action of catalyst；Then, VA aldehyde reacts life with another part phosphonium ylide
At target product beta carotene；Intermediate aldehydes and phosphonium ylide are to consume side below in basic compound catalysis to generate, can be effective
Avoid the generation of the by-products such as aldehyde self-condensation.
The vfanadium compound can be selected from VO (acac)2、VO(OAc)2、VO(hfac)2、NH4VO3、NaVO3、KVO3、V2O5、VO
(OEt)3、VO(OPr)3、VO(Oi-Pr)3At least one of Deng, preferably VO (acac)2、VO(OAc)2、NH4VO3、V2O5In
At least one, preferably VO (acac)2。
The molecular sieve can be selected from least one of 3A molecular sieve, 4A molecular sieve, 5A molecular sieve etc..
The alkali compounds can be selected from alkali metal hydroxide, alkali metal alcoholates, alkali carbonate, alkali metal phosphoric acid
At least one of salt, alkali metal acylate etc.；It is preferred that K2CO3、Na2CO3、Cs2CO3、Li2CO3、NaOH、KOH、LiOH、
K3PO4、Na3PO4, at least one of BuOK, BuONa, NaOAc, KOAc, EtONa, EtOK etc., preferably K2CO3、NaOH、
At least one of KOH, EtONa, BuONa etc..
The phase transfer catalyst can be selected from 12- crown ether -4,15 crown ethers -5,18- crown ether -6, dibenzo-18-crown-6 (DB18C6),
Average molecular weight is 1000 polyethylene glycol, average molecular weight is 1500 polyethylene glycol, average molecular weight is 2000 polyethylene glycol, three
At least one of contracting tetraethylene glycol, tetraethylene-glycol dimethyl ether etc..
The organic solvent can be selected from toluene, methylene chloride, chloroform, benzene, dichloroethanes, n-hexane, tetrahydrofuran, petroleum
At least one of ether, methyl ether, methyl tert-butyl ester etc..
The molar ratio of organic phosphonium salt and catalyst can be 1 ︰ (0.01~1).
The ratio that organic phosphonium salt is in terms of mM (mmol) and molecular sieve is in terms of quality gram (g) can for 1 ︰ (0.1~
0.5)。
The molar ratio of organic phosphonium salt and alkali can be 1 ︰ (1.5~3).
The molar ratio of organic phosphonium salt and phase transfer catalyst can be 1 ︰ (1.5~3).
The molal volume ratio (mol/L) of organic phosphonium salt and organic solvent can be 1 ︰ (10~30).
The reaction temperature of the coupling reaction can be 10~60 DEG C, preferably 25~40 DEG C.
The reaction time of the coupling reaction can be 2~8h；It is preferred that 2~4h.
After the intermolecular oxidative coupling reaction, solid can be removed to the cooling layering of reaction solution, organic phase washing is concentrated back
Receive the mixture that obtained red solid after solvent is beta carotene and phosphine oxide compound composition, the mixture with alcohols (such as
Methanol) it removes and removes phosphine oxide compound, it then carries out recrystallizing or heating in a solvent, then carry out various cis- mixtures to being all-trans
Rearrangement processing of formula structure etc..
The present invention has the following advantages that：
1, it is safe from harm as oxidant to environment using clean and environmental protection, economical and easily available, Portable safety oxygen-containing gas,
It is at low cost, it is conducive to industrialized production.
2, catalyst is done using vfanadium compound, significantly reduces the coupling reaction time；Co-catalyst is done using molecular sieve, is reduced
Catalyst usage amount improves catalytic oxidation effect, reduces the discharge of metal ion waste water.
3, carbonate can be used in reaction, avoids using the organic alkalis compound such as LDA, butyl lithium, Sodamide.
4, reaction is using the solid-liquid two-phase reaction system constituted in organic solvent, phase transfer catalyst and alkali compounds
Middle progress can be effectively controlled the solubility of alkali in reaction organic phase, avoid VA aldehyde self-condensation and the production of the excessively high initiation of alkali concentration
The side reactions such as object molecular conjugation double bond is destroyed improve target product yield；
5, reaction condition is mild, does not need to be limited by harsh anhydrous and oxygen-free reaction condition, easy to operate, safety coefficient
It is high；The three wastes that reaction generates are easily processed, and it is more environmentally protective to compare other methods.
Specific embodiment
Below with reference to embodiment, the present invention is further illustrated.
Embodiment 1：Coupling reaction prepares beta carotene
90g vitamine A acetate oily (221.3 ten thousand IU/g, 0.208mol) and 48.4g aniline (0.52mol) is taken to be dissolved in
In 1100ml ethyl alcohol, it is made into vitamine A acetate-ethanol solution.218.2g triphenylphosphine is separately added into three-necked flask
(0.832mol) and 2300ml ethyl alcohol, is cooled to 10 DEG C hereinafter, the 31.0g concentrated sulfuric acid (0.316mol) is slowly added dropwise in dropping funel,
Control dropping temperature is 10 DEG C to be continued to stir 2h hereinafter, being added dropwise.Vitamine A acetate-ethanol solution, 25 DEG C of reactions are added
For 24 hours, vitamin A triphenyl phosphine dichloride solution is obtained.Then it is concentrated under reduced pressure, adds 200ml acetone solution, be put into refrigerator
It crystallizes for 24 hours, crystallization is filtered, washed, dries, and obtains vitamin A triphenylphosphine sulfate (similarly hereinafter).
By vitamin A triphenylphosphine sulfate (1.0mmol), VO (acac)2(0.1mmol), 3A molecular sieve (0.3g),
18- crown ether -6 (2.0mmol) and K2CO3(2.0mmol) is added in toluene (20ml), and reaction solution keeps the feelings of normal pressure in logical oxygen
6h is stirred to react at 40 DEG C under condition.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate vacuumized dense
Contracting.Obtained solid is target product beta carotene crude product, is heated at reflux being dissolved in n-hexane under this crude product nitrogen protection
12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline later；It adopts
It is analyzed (detection method is similarly hereinafter) with the method for GB5009.83-2016, content 99.0% (HPLC)；Total recovery 84%.
Embodiment 2
90g vitamine A acetate oily (221.3 ten thousand IU/g, 0.208mol) and 48.4g aniline (0.52mol) is taken to be dissolved in
In 1100ml ethyl alcohol, it is made into vitamine A acetate-ethanol solution.218.2g triphenylphosphine is separately added into three-necked flask
(0.832mol) and 2300ml ethyl alcohol is cooled to 10 DEG C, and 51.5ml concentrated hydrochloric acid (mass concentration is slowly added dropwise in dropping funel
37.5%, 0.624mol), control dropping temperature is 10 DEG C, is added dropwise and continues to stir 2h.Vitamine A acetate-ethyl alcohol is added
Solution, 25 DEG C of reactions for 24 hours, obtain vitamin A triphenyl phosphine dichloride solution.Then it is concentrated under reduced pressure, it is molten to add 200ml acetone
Solution, is put into refrigerator and crystallizes for 24 hours, and crystallization is filtered, washed, dries, and obtains vitamin A triphenylphosphine hydrogen bromide salt (similarly hereinafter).
By vitamin A triphenylphosphine hydrochloride (1.0mmol), VO (OAc)2(0.1mmol), 4A molecular sieve (0.3g), 18-
Crown ether -6 (2.0mmol) and EtONa (2.0mmol) are added in anhydrous methanol (20ml), and reaction solution keeps normal pressure in logical oxygen
In the case of be stirred to react 8h at 40 DEG C.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate vacuumized dense
Contracting.Obtained solid is target product beta carotene crude product, is heated at reflux being dissolved in n-hexane under this crude product nitrogen protection
12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline, contain later
Measure 99.1% (HPLC)；Total recovery 70%.
Embodiment 3
90.96g retinol (294.97 ten thousand IU/g, 0.281mol) and 15.4ml pyridine (0.191mol) is taken to be dissolved in
500ml methanol is made into retinol-methanol solution.Triphenylphosphine 77.4g (0.295mol) is separately added into three-necked flask
With 1000ml methanol, it is cooled to 0 DEG C, dropping funel is slowly added dropwise 45.4ml HBr (mass concentration 47%, 0.393mol), control
Dropping temperature processed is 0 DEG C, is added dropwise and continues to stir 2h, retinol-methanol solution is added, 10 DEG C of reactions are for 24 hours.Then subtract
Pressure concentration, adds 200ml acetone solution, is put into refrigerator and crystallizes for 24 hours, and crystallization is filtered, washed, dries, and obtains vitamin A three
Phenylphosphine hydrogen bromide salt (similarly hereinafter).
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), NH4VO3(0.1mmol), 4A molecular sieve (0.3g), 12-
Crown ether -4 (2.0mmol) and KOH (2.0mmol) are added in tetrahydrofuran (20ml), and reaction solution keeps the feelings of normal pressure in logical oxygen
5h is stirred to react at 40 DEG C under condition.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate vacuumized dense
Contracting.Obtained solid is target product beta carotene crude product, is heated at reflux being dissolved in n-hexane under this crude product nitrogen protection
12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline, contain later
Measure 98.7% (HPLC)；Total recovery 72%.
Embodiment 4
Take 90g vitamine A acetate oily (221.3 ten thousand IU/g, 0.208mol) and 22.7g para-aminophenol (0.208mol)
It is dissolved in 380ml ethylene glycol, is made into vitamine A acetate-ethylene glycol solution.95.5g triphen is separately added into three-necked flask
Base phosphine (0.364mol) and 880ml ethylene glycol are cooled to 10 DEG C, and 277.4g benzene sulfonic acid ethylene glycol solution is slowly added dropwise in dropping funel
(mass concentration 19.6%, 0.344mol), control dropping temperature are 10 DEG C, are added dropwise and continue to stir 2h.Vitamin A vinegar is added
Acid esters-ethylene glycol solution, 25 DEG C of reaction 40h, obtains vitamin A triphenylphosphine benzene sulfonate solution.Then it is concentrated under reduced pressure, then plus
Enter 200ml acetone solution, be put into refrigerator and crystallize for 24 hours, crystallization is filtered, washed, dries, by vitamin A triphenylphosphine benzene sulfonic acid
Salt (similarly hereinafter).
By vitamin A triphenylphosphine benzene sulfonate (1.0mmol), V2O5(0.1mmol), 3A molecular sieve (0.3g), 18- hat
Ether -6 (2.0mmol) and BuONa (2.0mmol) are added in methylene chloride (20ml), and reaction solution keeps the feelings of normal pressure in logical oxygen
6h is stirred to react at 40 DEG C under condition.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate vacuumized dense
Contracting.Obtained solid is target product beta carotene crude product, is heated at reflux being dissolved in n-hexane under this crude product nitrogen protection
12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline, contain later
Measure 99.2% (HPLC)；Total recovery 68%.
Embodiment 5
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), VO (acac)2(0.1mmol), 3A molecular sieve (0.3g),
18- crown ether -6 (2.0mmol) and KOH (2.0mmol) are added in toluene (20ml), and reaction solution is the case where logical oxygen keeps normal pressure
Under be stirred to react 4h at 40 DEG C.Later, it is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate is vacuumized
Concentration.Obtained solid is target product beta carotene crude product, and reflux in n-hexane will be dissolved under this crude product nitrogen protection and is added
Hot 12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline later,
Content 99.0% (HPLC)；Total recovery 91%.
Embodiment 6
By vitamin A triphenylphosphine hydrochloride (1.0mmol), VO (OAc)2(0.1mmol), 4A molecular sieve (0.3g), 15-
Crown ether -5 (2.0mmol) and K2CO3(2.0mmol) is added in n-hexane (20ml), and above-mentioned reaction solution keeps normal pressure in logical oxygen
In the case of be stirred to react 5h at 40 DEG C.Later, it is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate is taken out
Vacuum concentration.Obtained solid is target product beta carotene crude product, will be dissolved in n-hexane and returns under this crude product nitrogen protection
Stream heating 12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain peony knot later
Crystalline substance, content 98.5% (HPLC)；Total recovery 74%.
Embodiment 7
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), VO (acac)2(0.1mmol), 3A molecular sieve (0.3g),
The methyl tert-butyl ester (20ml) is added in polyethylene glycol (0.01mmol) and KOH (2.5mmol), and reaction solution keeps micro-positive pressure in logical oxygen
In the case where be stirred to react 7h at 40 DEG C.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate is vacuumized
Concentration.Obtained solid is target product beta carotene crude product, and reflux in n-hexane will be dissolved under this crude product nitrogen protection and is added
Hot 12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline later,
Content 98.9% (HPLC)；Total recovery 82%.
Reaction substrate used by Examples 1 to 7 and corresponding yield are as shown in table 1.
Table 1
Embodiment 8
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), VO (acac)2(1.0mmol), 3A molecular sieve (0.1g),
18- crown ether -6 (1.5mmol) and KOH (1.5mmol) are added in toluene (30ml), and reaction solution keeps the feelings of micro-positive pressure in logical oxygen
6h is stirred to react at 10 DEG C under condition.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate vacuumized dense
Contracting.Obtained solid is target product beta carotene crude product, is heated at reflux being dissolved in n-hexane under this crude product nitrogen protection
12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline, contain later
Measure 98.8% (HPLC)；Total recovery 75%.
Embodiment 9
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), VO (acac)2(0.01mmol), 3A molecular sieve
(0.5g), 18- crown ether -6 (3.0mmol) and KOH (3.0mmol) are added in toluene (10ml), and reaction solution keeps micro- in logical oxygen
2h is stirred to react at 60 DEG C in the case where positive pressure.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate is taken out
Vacuum concentration.Obtained solid is target product beta carotene crude product, will be dissolved in n-hexane and returns under this crude product nitrogen protection
Stream heating 12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain peony knot later
Crystalline substance, content 99.0% (HPLC)；Total recovery 77%.
Embodiment 10
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), VO (acac)2(0.05mmol), 3A molecular sieve
(0.5g), 18- crown ether -6 (3.0mmol) and KOH (2.2mmol) are added in toluene (15ml), and reaction solution keeps micro- in logical oxygen
3h is stirred to react at 25 DEG C in the case where positive pressure.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate is taken out
Vacuum concentration.Obtained solid is target product beta carotene crude product, will be dissolved in n-hexane and returns under this crude product nitrogen protection
Stream heating 12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain peony knot later
Crystalline substance, content 98.7% (HPLC)；Total recovery 80%.
Embodiment 11
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), VO (acac)2(0.07mmol), 3A molecular sieve
(0.4g), 18- crown ether -6 (2.5mmol) and KOH (2.5mmol) are added in toluene (25ml), and reaction solution keeps micro- in logical oxygen
2h is stirred to react at 50 DEG C in the case where positive pressure.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate is taken out
Vacuum concentration.Obtained solid is target product beta carotene crude product, will be dissolved in n-hexane and returns under this crude product nitrogen protection
Stream heating 12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain peony knot later
Crystalline substance, content 98.5% (HPLC)；Total recovery 83%.
Embodiment 12
By vitamin A triphenylphosphine hydrogen bromide salt (1.0mmol), VO (acac)2(1.0mmol), 3A molecular sieve (0.2g),
18- crown ether -6 (2.2mmol) and KOH (3.0mmol) are added in toluene (20ml), and reaction solution keeps the feelings of micro-positive pressure in logical oxygen
3h is stirred to react at 30 DEG C under condition.It is cooled to room temperature to reaction solution, is filtered to remove solid residue, filtrate vacuumized dense
Contracting.Obtained solid is target product beta carotene crude product, is heated at reflux being dissolved in n-hexane under this crude product nitrogen protection
12h carries out various cis-compounds and handles to alltrans structural isomerismization, and cold filtration, dries to obtain deep red crystalline later, pure
Degree is 99.1% (HPLC)；Total recovery 84%.
Reaction substrate feed ratio and corresponding yield used by embodiment 9~12 are as shown in table 2.
Table 2
Embodiment 13~17
When being added without molecular sieve, embodiment 13~17 is implemented respectively in a manner of identical with embodiment 8~12 respectively；
The yield of corresponding product is as shown in table 3.
Table 3
As can be seen from Table 3, when not applicable molecular sieve, yield is greatly lowered；Thus molecular sieve is demonstrated to this hair
Bright is essential.Molecular sieve has many advantages, such as that surface area is big, pore size distribution is uniform, surface chemical property is abundant, is catalyst carrier
A kind of ideal chose, addition molecular sieve can reduce catalyst vfanadium compound usage amount in reaction system, and may be implemented in often
The progress of warm or lower heating temperature situation catalytically oxidative coupling reaction, in addition molecular sieve ontology is also easy from reaction system
Separate reuse.
Embodiment 18~19
When carrying out under air atmosphere, embodiment 18 is implemented respectively in a manner of identical with embodiment 11~12 respectively
~19；The yield of corresponding product is as shown in table 4.
Table 4
As shown in Table 4, when reaction carries out under air atmosphere, reaction can not carry out or yield is extremely low, thus proves
Oxygen atmosphere is for of the invention essential.Oxygen is as oxidant, and at low cost, raw material is easy to get, economical and practical, is suitable for industrialization
Production.
Embodiment 20~22
The situation for not adding catalyst vfanadium compound in reaction is investigated, mode identical with embodiment 10~12 is distinguished respectively
Implement embodiment 20~22；The yield of corresponding product is as shown in table 5.
Table 5
As shown in Table 5, when reacting when not adding vfanadium compound, the very slow of progress is reacted, target product yield is very low,
Thus prove vfanadium compound for the importance of raising reaction speed and conversion ratio.Vanadium-containing compound is a kind of thermal stability and change
The all very high compound of stability is learned, while being also a kind of excellent catalyst for selective oxidation, it can be selectively by oxidation product
Rest on aldehydes or ketones and without deep oxidation.Vanadium-containing compound is added in the present invention and makees the catalyst reacted, can greatly be contracted
Short oxygen carries out the time required for coupling reaction as oxidant, while improving the selectivity of reaction, prevents deep oxidation；Oxygen
Other impurities are not introduced during changing, product can be easily separated.
In the present invention, polyethers phase transfer catalyst, which is added, can cause the reaction in heterogeneous reaction system between substrate；Gu
The formed complex compound of state alkali compounds and be dissolved in organic phase participate in reaction, effectively control organic phase in alkali dissolution
Degree inhibits the generation of by-product while promoting reaction to carry out, increase the yield of kind of product, to reach the mesh for improving yield
's.
Claims (10)
1. the synthetic method of beta carotene, it is characterised in that specific step is as follows for it：
Organic phosphonium salt is prepared by retinol or derivatives thereof, in the presence of vfanadium compound catalyst and molecular sieve, in oxygen
During atmosphere is enclosed, intermolecular oxidative coupling reaction occurs, obtains beta carotene.
2. the synthetic method of beta carotene as described in claim 1, it is characterised in that the intermolecular oxidative coupling reaction is having
It is carried out in the solid-liquid two-phase reaction system that solvent, phase transfer catalyst and alkali compounds are constituted, reaction route is as follows：
Wherein, R1, R2, R3 are aromatic group, aliphatic, alicyclic group, and described R1, R2, R3 are phenyl, benzyl, hexamethylene
Base or butyl；It is described for the acid group of inorganic acid or the acid group of organic acidSelected from bisulfate ion, sulfate radical, tetrafluoro boron
It is acid group, phosphate radical, acetate, tosylate, a kind of in benzene sulfonic acid root, preferably chloride ion, bromide ion or iodide ion.
3. the synthetic method of beta carotene as described in claim 1, it is characterised in that the vfanadium compound is selected from VO (acac)2、
VO(OAc)2、VO(hfac)2、NH4VO3、NaVO3、KVO3、V2O5、VO(OEt)3、VO(OPr)3、VO(Oi-Pr)3In at least one
Kind.
4. the synthetic method of beta carotene as described in claim 1, it is characterised in that the molecular sieve is selected from 3A molecular sieve, 4A
At least one of molecular sieve, 5A molecular sieve.
5. the synthetic method of beta carotene as claimed in claim 2, it is characterised in that the alkali compounds is selected from alkali metal hydrogen
At least one of oxide, alkali metal alcoholates, alkali carbonate, alkali metal phosphate, alkali metal acylate；It is preferred that
K2CO3、Na2CO3、Cs2CO3、Li2CO3、NaOH、KOH、LiOH、K3PO4、Na3PO4、BuOK、BuONa、NaOAc、KOAc、
At least one of EtONa, EtOK.
6. the synthetic method of beta carotene as claimed in claim 2, it is characterised in that the phase transfer catalyst is preced with selected from 12-
Ether -4,15 crown ethers -5,18- crown ether -6, dibenzo-18-crown-6 (DB18C6), the polyethylene glycol that average molecular weight is 1000, mean molecule
Measure the polyethylene glycol for 1500, the polyethylene glycol that average molecular weight is 2000, tetraethylene-glycol, tetraethylene-glycol dimethyl ether
At least one of.
7. the synthetic method of beta carotene as claimed in claim 2, it is characterised in that the organic solvent is selected from toluene, dichloro
At least one of methane, chloroform, benzene, dichloroethanes, n-hexane, tetrahydrofuran, petroleum ether, methyl ether, methyl tert-butyl ester.
8. the synthetic method of beta carotene as claimed in claim 1 or 2, it is characterised in that organic phosphonium salt and catalyst
Molar ratio is 1 ︰ (0.01~1)；Organic phosphonium salt by mM in terms of and ratio of the molecular sieve in terms of quality gram can for 1 ︰ (0.1~
0.5)；The molar ratio of organic phosphonium salt and alkali can be 1 ︰ (1.5~3)；Mole of organic phosphonium salt and phase transfer catalyst
Than that can be (1.5~3) 1 ︰；The molal volume ratio of organic phosphonium salt and organic solvent can be 1 ︰ (10~30), wherein organic phosphine
Salt is calculated in mol, and organic solvent is risen with volume and calculated.
9. the synthetic method of beta carotene as claimed in claim 1 or 2, it is characterised in that the reaction temperature of the coupling reaction
It is 10~60 DEG C, preferably 25~40 DEG C；The reaction time of the coupling reaction is 2~8h；It is preferred that 2~4h.
10. the synthetic method of beta carotene as claimed in claim 1 or 2, it is characterised in that the intermolecular oxidative coupling reaction
Afterwards, solid is removed to the cooling layering of reaction solution, the red solid obtained after organic phase washing, concentration and recovery solvent is β-Hu Luo
Bu Su and phosphine oxide compound composition mixture, the mixture alcohols washout remove phosphine oxide compound, then carry out recrystallization or
It is heated in solvent, then carries out various cis- mixtures and handled to the rearrangement of alltrans structure, the preferred methanol of alcohols.
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| CN110452147A (en) * | 2019-07-30 | 2019-11-15 | 万华化学集团股份有限公司 | A kind of preparation method of beta carotene |
| CN113321604A (en) * | 2021-06-23 | 2021-08-31 | 万华化学集团股份有限公司 | Preparation method of beta-carotene with high all-trans content |
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| CN110452147A (en) * | 2019-07-30 | 2019-11-15 | 万华化学集团股份有限公司 | A kind of preparation method of beta carotene |
| CN110452147B (en) * | 2019-07-30 | 2021-07-23 | 万华化学集团股份有限公司 | Preparation method of beta-carotene |
| WO2022056827A1 (en) * | 2020-09-18 | 2022-03-24 | 厦门金达威维生素有限公司 | METHOD FOR PREPARING β-CAROTENE |
| CN113321604A (en) * | 2021-06-23 | 2021-08-31 | 万华化学集团股份有限公司 | Preparation method of beta-carotene with high all-trans content |
| CN113321604B (en) * | 2021-06-23 | 2023-01-13 | 万华化学集团股份有限公司 | Preparation method of beta-carotene |
| CN113651743A (en) * | 2021-08-30 | 2021-11-16 | 万华化学集团股份有限公司 | Preparation method of beta-carotene |
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| CN113651743B (en) * | 2021-08-30 | 2023-03-14 | 万华化学集团股份有限公司 | Preparation method of beta-carotene |
| CN114534729A (en) * | 2022-03-07 | 2022-05-27 | 万华化学集团股份有限公司 | Catalyst, preparation method thereof and application thereof in preparing beta-carotene by electrochemical method |
| CN114534729B (en) * | 2022-03-07 | 2024-05-03 | 万华化学集团股份有限公司 | Catalyst, preparation method thereof and application of catalyst in preparation of beta-carotene by electrochemical method |
| CN114957075A (en) * | 2022-06-13 | 2022-08-30 | 万华化学集团股份有限公司 | Preparation method of beta-carotene |
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