CN109232178A - Prepare the new method of high-purity hydroxytyrosol - Google Patents
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- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
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Abstract
The invention discloses the new methods of preparation high-purity hydroxytyrosol, belong to pharmaceutical chemistry synthesis technical field, the specific steps of this method are as follows: be uniformly mixed lithium aluminium hydride reduction with solvent, then 3 are added in batches, 4- dihydroxyphenyl acetic acid is reacted, reaction solution after completion of the reaction is placed at 0 DEG C, water and hydrochloric acid solution is slowly added dropwise, drop is extracted with ethyl acetate after finishing, merge organic phase, then washed with sodium bicarbonate aqueous solution, then filters desalination after anhydrous magnesium sulfate is dry, evaporating solvent under reduced pressure, obtaining light yellow oil is hydroxytyrosol.Have the beneficial effect that the raw material of novel preparation method of the present invention is easy to get, it is at low cost, it is easy to operate, can step reduction 3,4-Dihydroxyphenylacetic acid be hydroxytyrosol, reaction rate is fast, the yield of target product is high, can be prepared by the hydroxytyrosol of high-purity without column chromatographic purifying, is suitble to industrialized production.
Description
Technical field
The present invention relates to pharmaceutical chemistry synthesis technical fields, more particularly, to the new method of preparation high-purity hydroxytyrosol.
Background technique
Hydroxytyrosol, also known as Hydroxytyrosol are a kind of Polyphenols chemical combination in olive with strong anti-oxidation
Object, while being also the metabolite of dopamine in animal brain.Studies have shown that hydroxytyrosol has good bioactivity, mainly
Antimicrobial acivity including wide spectrum prevents the coup injury of a variety of free radicals, prevents diabetes and improves adipose tissue to pancreas
The sensibility of island element reduces the lesion range of atherosclerosis and prevents myocardial ischemia/reperfusion injury, improves beta amyloid
Protein induced Alzheimer's disease and inhibition tumor proliferation etc..External many mechanisms are using hydroxytyrosol as additive
It is added in health care product and food, discovery plays the role of good anti-aging and prevention disease.
Currently, hydroxytyrosol is mainly obtained as following manner: (1) extracting hydroxyl junket from waste liquid caused by squeezing olive oil
Alcohol.The advantages of this method is to carry out waste utilization to waste water caused by production olive oil, reduces the pollution to environment.But this
Method need to consume a large amount of solvents, and hydroxytyrosol yield is lower, be not suitable for industrialized production；(2) it is obtained using biological fermentation process
Hydroxytyrosol.This method is related to genetic engineering bacterium, higher to technical requirements, and the production cycle is long, and technology is also immature at present；(3)
Hydroxytyrosol is prepared using chemically synthesized method.The artificial synthesis of hydroxytyrosol reported in the literature has in recent years:
1) it is Material synthesis hydroxytyrosol with 3,4- dimethoxy benzyl carbinol, synthetic route is as follows:
.The method final step deprotection reaction yield only has 10%, and synthesis step is longer, and cost is excessively high.But it uses
It is directly also undesirable to 3,4- dimethoxy benzyl carbinol deprotection synthesis of hydroxy tyrosol yield under tin trichloride catalysis, and react not
It is easy to control, Friedel-Crafts side reaction easily occurs.
2) Bovicelli etc. reports one using tyrosol as the route of Material synthesis hydroxytyrosol, and synthetic route is as follows:
A)LiAlH4TH F；B)C H2Cl230%HCl；C)wheat germ lipase pH 7.5
.The route need to introduce a hydroxyl on phenyl ring, and it is numerous that this is related to processes, the step such as hydroxyl protection and deprotection
It is trivial, also use Boron tribromide etc. in the process and do not allow easy-operating reagent, this method no matter laboratory synthesis or industrial production all
Seldom use.
3) permitted superfine report another kind using catechol as the method for Material synthesis hydroxytyrosol, synthetic route is as follows:
.Not only reaction step is long for the route, while using extremely hazardous Boron tribromide, reacts more violent, laboratory
Less use.
4) prolong and wait forever with 3,4- dimethoxyphenylacetic acid as starting material, synthetic route is as follows:
, but this reaction uses the strong hydrogen bromide of corrosivity and inflammable and explosive metallic sodium, therefore has certain risk.
It is presently available for the synthetic route (WO2008128629) that industrial Royal DSM company delivers, but this
Technique, which exists, expends that a large amount of solvents, the reaction time is longer, vacuum distillation temperature is excessively high (2000C) is not suitable for large-batch high-purity hydroxyl
The production of base tyrosol product.It is, thus, sought for a kind of new method for preparing high-purity hydroxytyrosol.
Summary of the invention
It is an object of the invention to overcome existing technological deficiency, a kind of raw material is provided and is easy to get, it is at low cost, it is easy to operate,
Can step reduction 3,4-Dihydroxyphenylacetic acid be hydroxytyrosol, reaction rate is fast, and the yield of target product is high, chromatographs without column
Purifying can be prepared by the new method of the preparation high-purity hydroxytyrosol of the hydroxytyrosol of high-purity.
The present invention in view of the above technology in the problem of mentioning, the technical solution taken are as follows:
The new method of high-purity hydroxytyrosol is prepared, synthetic route is as follows:
Preferably, preparation high-purity hydroxytyrosol new method specifically includes the following steps:
Step 1: lithium aluminium hydride reduction being put into dry single port bottle, solvent is added, be sufficiently mixed uniform that concentration is 1.5-
The solution of 2.0mol/L, it is spare；
Step 2: being at 0 DEG C to step 1 that 3,4-Dihydroxyphenylacetic acid is added portionwise in solution, removed after addition
Ice bath reacts 2-20h at 20-100 DEG C；
Step 3: reaction solution after completion of the reaction being placed at 0 DEG C, water and concentration is slowly added dropwise as the hydrochloric acid of 1.5-2.5M
Solution, drop are extracted with ethyl acetate 2-4 times after finishing, and merge organic phase, are then washed 2-4 times with sodium bicarbonate aqueous solution, then pass through
Desalination is filtered after anhydrous magnesium sulfate is dry, evaporating solvent under reduced pressure, obtaining light yellow oil is hydroxytyrosol, the preparation method
Easy to operate, not high to working condition and equipment requirement, reaction process step is short, selectivity is good, is washed using saturated sodium bicarbonate
Unreacted raw material can be removed by washing, and the hydroxytyrosol of high-purity has been directly obtained without column chromatography, reduce organic solvent use
Amount, is greatly saved preparation time, can carry out large-scale industrial production, and the purity of hydroxytyrosol and yield are higher.
Further preferably, the pantothenic acid of the aluminium chloride in lithium aluminium hydride reduction containing 0.023-0.025% and 0.012-0.016%
Calcium, the mass ratio of left-handed calcium pantothenate and dextro calcium pantothenate is 1:90-95 in calcium pantothenate, and the addition of aluminium chloride and calcium pantothenate can be into
One step improves the reducing power and reduction selectivity of lithium aluminium hydride reduction, improves lithium aluminium hydride reduction positively charged atom into polarity unsaturated bond
Attack rate, enable 3,4-Dihydroxyphenylacetic acid faster, be more effectively converted into hydroxytyrosol, while calcium pantothenate add
Enter can be avoided to generate Al (OH)3Jelly enables reduction reaction to go on smoothly, and reduces the use of lithium aluminium hydride reduction and solvent
Amount, reduces the production cost of hydroxytyrosol, has good promotional value, and current product is easily separated, but also after
The loss of product is reduced when processing, and furthermore collaboration increasing can occur for the special proportion of left-handed calcium pantothenate and dextro calcium pantothenate in calcium pantothenate
Beneficial effect, the cooperative gain effect can reduce the negatively charged amount of carboxylic acid group charge-site institute, so as to reduce dipole moment, dipole
The reduction of square can further improve protonation ability, and the carbonyl of carboxylic acid is protonated, the electrophilicity of carbonyl carbon is enhanced, and make anti-
It answers rate to accelerate, improves the efficiency of reduction reaction.
Further preferably, be benzene or 1 with solvent in step 1,2- dichloroethanes or methylene chloride or Isosorbide-5-Nitrae-dioxane or
Ether or tetrahydrofuran.
Further preferably, the molar ratio of lithium aluminium hydride reduction and 3,4-Dihydroxyphenylacetic acid be 4-6:1, above-mentioned lithium aluminium hydride reduction and 3,
The reasonable molar ratio of 4- dihydroxyphenyl acetic acid can enable one step of lithium aluminium hydride reduction reduction 3,4-Dihydroxyphenylacetic acid be hydroxytyrosol,
Reaction route is greatly shortened, synthesis technology is optimized, high income is environmental-friendly, and then solution hydroxytyrosol preparation condition complexity,
The problems such as not easy to control, the high requirements on the equipment, step be more, expensive raw material price, and lithium aluminium hydride reduction also it is controllable react into
Journey and the selectivity with certain space, so that the yield of target product is high.
Further preferably, the sodium bicarbonate aqueous solution washed in step 3 is saturated sodium bicarbonate solution.
Compared with the prior art, the advantages of the present invention are as follows: 1) novel preparation method of of the present invention hydroxytyrosol easy to operate,
Not high to working condition and equipment requirement, reaction process step is short, selectivity is good, optimizes synthesis technology, high income, environment friend
It is good, and then solve complicated hydroxytyrosol preparation condition, not easy to control, the high requirements on the equipment, the more, expensive raw material price of step etc.
Problem；2) reducing power of lithium aluminium hydride reduction of the invention and reduction selectivity it is stronger, enable 3,4-Dihydroxyphenylacetic acid more
Fastly, it is more effectively converted into hydroxytyrosol, and reduction reaction is gone on smoothly, reduces the use of lithium aluminium hydride reduction and solvent
Amount, reduces the production cost of hydroxytyrosol, has good promotional value；3) present invention is removed using saturated sodium bicarbonate washing
Unreacted raw material has directly obtained the hydroxytyrosol of high-purity without column chromatography, has reduced consumption of organic solvent, greatly save
Preparation time, can carry out large-scale industrial production.
Specific embodiment
The present invention program is described further below by embodiment:
Embodiment 1:
The new method of high-purity hydroxytyrosol is prepared, synthetic route is as follows:
The new method of above-mentioned preparation high-purity hydroxytyrosol specifically includes the following steps:
Step 1: lithium aluminium hydride reduction being put into dry single port bottle, solvent is added, be sufficiently mixed uniform that concentration is
The solution of 1.5mol/L, it is spare；
Step 2: being at 0 DEG C to step 1 that 3,4-Dihydroxyphenylacetic acid is added portionwise in solution, removed after addition
Ice bath reacts 2h at 100 DEG C；
Step 3: reaction solution after completion of the reaction is placed at 0 DEG C, the hydrochloric acid solution that water and concentration are 2.5M is slowly added dropwise,
Drop is extracted with ethyl acetate 2 times after finishing, and merges organic phase, is then washed 4 times with sodium bicarbonate aqueous solution, then through anhydrous magnesium sulfate
Desalination is filtered after drying, evaporating solvent under reduced pressure, obtaining light yellow oil is hydroxytyrosol, and the preparation method is easy to operate,
Not high to working condition and equipment requirement, reaction process step is short, selectivity is good, can be removed using saturated sodium bicarbonate washing
Unreacted raw material has directly obtained the hydroxytyrosol of high-purity without column chromatography, has reduced consumption of organic solvent, greatly save
Preparation time, can carry out large-scale industrial production, and the purity of hydroxytyrosol and yield are higher.
Containing 0.023% aluminium chloride and 0.016 calcium pantothenate in above-mentioned lithium aluminium hydride reduction, in calcium pantothenate left-handed calcium pantothenate and
The mass ratio of dextro calcium pantothenate is 1:90, and the addition of aluminium chloride and calcium pantothenate can further improve the reducing power of lithium aluminium hydride reduction
With reduction selectivity, the attack rate of lithium aluminium hydride reduction positively charged atom into polarity unsaturated bond is improved, so that 3,4- dihydroxy
Phenylacetic acid can faster, be more effectively converted into hydroxytyrosol, while calcium pantothenate addition can be avoided and can generate Al (OH)3Glue
Shape object, enables reduction reaction to go on smoothly, and reduces the dosage of lithium aluminium hydride reduction and solvent, reduces being produced into for hydroxytyrosol
This, has good promotional value, and current product is easily separated, but also the loss of product is reduced when post-processing, this
Cooperative gain effect can occur for the special proportion of left-handed calcium pantothenate and dextro calcium pantothenate in outer calcium pantothenate, which can
The negatively charged amount of carboxylic acid group charge-site institute is reduced, so as to reduce dipole moment, the reduction of dipole moment can be mentioned further
The carbonyl of carboxylic acid is protonated, enhances the electrophilicity of carbonyl carbon, accelerate reaction rate by high proton ability, and it is anti-to improve reduction
The efficiency answered.
It with solvent is benzene in above-mentioned steps 1.
The molar ratio of above-mentioned lithium aluminium hydride reduction and 3,4-Dihydroxyphenylacetic acid is 4:1, above-mentioned lithium aluminium hydride reduction and 3,4- dihydroxy
The reasonable molar ratio of phenylacetic acid can enable one step of lithium aluminium hydride reduction reduction 3,4-Dihydroxyphenylacetic acid be hydroxytyrosol, greatly shorten
Reaction route optimizes synthesis technology, and high income is environmental-friendly, and then it is complicated, not easily-controllable to solve hydroxytyrosol preparation condition
The problems such as system, the high requirements on the equipment, step be more, expensive raw material price, and the process and tool of the also controllable reaction of lithium aluminium hydride reduction
There is the selectivity of certain space, so that the yield of target product is high.
The sodium bicarbonate aqueous solution washed in above-mentioned steps 3 is saturated sodium bicarbonate solution.
Embodiment 2:
The new method of high-purity hydroxytyrosol is prepared, synthetic route is as follows:
The new method of above-mentioned preparation high-purity hydroxytyrosol specifically includes the following steps:
Step 1: lithium aluminium hydride reduction being put into dry single port bottle, solvent is added, be sufficiently mixed uniform that concentration is
The solution of 1.8mol/L, it is spare；
Step 2: being at 0 DEG C to step 1 that 3,4-Dihydroxyphenylacetic acid is added portionwise in solution, removed after addition
Ice bath reacts 12h at 60 DEG C；
Step 3: reaction solution after completion of the reaction is placed at 0 DEG C, the hydrochloric acid solution that water and concentration are 2.0M is slowly added dropwise,
Drop is extracted with ethyl acetate 3 times after finishing, and merges organic phase, is then washed 3 times with sodium bicarbonate aqueous solution, then through anhydrous magnesium sulfate
Desalination is filtered after drying, evaporating solvent under reduced pressure, obtaining light yellow oil is hydroxytyrosol.
Containing 0.024% aluminium chloride and 0.014% calcium pantothenate in above-mentioned lithium aluminium hydride reduction, left-handed calcium pantothenate in calcium pantothenate
Mass ratio with dextro calcium pantothenate is 1:93；It with solvent is tetrahydrofuran in step 1；Lithium aluminium hydride reduction and 3,4- dihydroxy benzenes second
The molar ratio of acid is 5:1；The sodium bicarbonate aqueous solution washed in step 3 is saturated sodium bicarbonate solution.
Embodiment 3:
The new method of high-purity hydroxytyrosol is prepared, synthetic route is as follows:
The new method of above-mentioned preparation high-purity hydroxytyrosol specifically includes the following steps:
Step 1: lithium aluminium hydride reduction being put into dry single port bottle, solvent is added, be sufficiently mixed uniform that concentration is
The solution of 1.8mol/L, it is spare；
Step 2: being at 0 DEG C to step 1 that 3,4-Dihydroxyphenylacetic acid is added portionwise in solution, removed after addition
Ice bath reacts 12h at 60 DEG C；
Step 3: reaction solution after completion of the reaction is placed at 0 DEG C, the hydrochloric acid solution that water and concentration are 2.0M is slowly added dropwise,
Drop is extracted with ethyl acetate 3 times after finishing, and merges organic phase, is then washed 3 times with sodium bicarbonate aqueous solution, then through anhydrous magnesium sulfate
Desalination is filtered after drying, evaporating solvent under reduced pressure, obtaining light yellow oil is hydroxytyrosol, is contained in above-mentioned ethyl acetate
8.9 ‰ N- Phenylpyrrolidine, 1.3 ‰ dimethyl carbonate add N- Phenylpyrrolidine, the carbon of special proportion in ethyl acetate
The withholding ability to hydroxytyrosol can be enhanced in dimethyl phthalate, and the ethyl acetate and hydrone of polarity very little are mainly with dipole-idol
Extremely this relatively weak interaction combines, on the one hand, N- Phenylpyrrolidine in ethyl acetate, dimethyl carbonate presence can
The polarity of water solution system is further enhanced, and keeps the solubility of ethyl acetate smaller, reduces tyrosol phenolic acid ester type compound
It is scattered in the amount of the ethyl acetate in water phase, on the other hand, according to similar compatibility principle, in dimethyl carbonate and ethyl acetate
Ester group can increase solubility of the hydroxytyrosol in ethyl acetate to a certain extent, so that reducing hydroxytyrosol passes through saturation
It scatters and disappears caused by sodium bicarbonate aqueous solution, the final yield and yield for improving hydroxytyrosol reduces preparation cost.
Containing 0.024% aluminium chloride and 0.014% calcium pantothenate in above-mentioned lithium aluminium hydride reduction, left-handed calcium pantothenate in calcium pantothenate
Mass ratio with dextro calcium pantothenate is 1:93；It with solvent is tetrahydrofuran in step 1；Lithium aluminium hydride reduction and 3,4- dihydroxy benzenes second
The molar ratio of acid is 5:1；The sodium bicarbonate aqueous solution washed in step 3 is saturated sodium bicarbonate solution.
Embodiment 4:
Lithium aluminium hydride reduction (3.33g, 225mmol, 5equiv) is put into dry single port bottle, 125mL tetrahydrofuran is added
It is placed on stirring and dissolving at 0 DEG C.3,4-Dihydroxyphenylacetic acid (3.0g, 45mmol, 1.0equiv) is weighed, is added portionwise above-mentioned molten
In liquid, ice bath is removed in low temperature charging recession, reacts 6h at 60 DEG C, places reaction liquid at 0 DEG C, water is slowly added dropwise and 2M hydrochloric acid is molten
Liquid, drop are repeatedly extracted after finishing with ethyl acetate, are merged organic phase, are washed with saturated sodium bicarbonate solution, anhydrous magnesium sulfate
It is filtered after drying, evaporating solvent under reduced pressure, obtains light yellow oil, as hydroxytyrosol, high performance liquid chromatograph detects purity
It is 95%, yield 74%.
Nmr spectrum data are as follows:1H-NMR(DMSO-d6, 600MHz, ppm): 8.68 (s, 1H ,-OH), 8.57 (s,
1H ,-OH), 6.59-6.63 (q, 2H), 6.43-6.45 (q, 1H), 4.55 (s, 1H ,-OH), 3.51 (t, 2H), 2.54 (t, 2H)
；13C-NMR(DMSO-d6, 150MHz, ppm): δ 144.9,143.4,130.3,119.5,116.3,115.4,62.7,38.6.
Embodiment 5:
Lithium aluminium hydride reduction (3.33g, 225mmol, 5equiv) is put into dry single port bottle, the anhydrous tetrahydro of 125mL is added
Furans is placed on stirring and dissolving at 0 DEG C.3,4-Dihydroxyphenylacetic acid (3.0g, 45mmol, 1.0equiv) is weighed, is added portionwise
It states in solution, ice bath is removed in low temperature charging recession, reacts 8h at 60 DEG C, places reaction liquid at 0 DEG C, water and 2M salt is slowly added dropwise
Acid solution, drop are repeatedly extracted after finishing with ethyl acetate, are merged organic phase, are washed with saturated sodium bicarbonate solution, anhydrous sulphur
It is filtered after sour magnesium is dry, evaporating solvent under reduced pressure, obtains light yellow oil, as hydroxytyrosol, high performance liquid chromatograph detection
Purity is 95%, yield 85%.
Embodiment 6:
Lithium aluminium hydride reduction (2.00g, 135mmol, 3equiv) is put into dry single port bottle, the anhydrous tetrahydro of 125mL is added
Furans is placed on stirring and dissolving at 0 DEG C.3,4-Dihydroxyphenylacetic acid (3.0g, 45mmol, 1.0equiv) is weighed, is added portionwise
It states in solution, ice bath is removed in low temperature charging recession, reacts 8h at 60 DEG C, places reaction liquid at 0 DEG C, water and 2M salt is slowly added dropwise
Acid solution, drop are repeatedly extracted after finishing with ethyl acetate, are merged organic phase, are washed with saturated sodium bicarbonate solution, anhydrous sulphur
It is filtered after sour magnesium is dry, evaporating solvent under reduced pressure, obtains light yellow oil, as hydroxytyrosol, high performance liquid chromatograph detection
Purity is 95%, yield 87%.
Embodiment 7:
Lithium aluminium hydride reduction (2.00g, 135mmol, 3equiv) is put into dry single port bottle, the anhydrous tetrahydro of 125mL is added
Furans is placed on stirring and dissolving at 0 DEG C.3,4-Dihydroxyphenylacetic acid (3.0g, 45mmol, 1.0equiv) is weighed, is added portionwise
It states in solution, ice bath is removed in low temperature charging recession, reacts 8h at 60 DEG C, places reaction liquid at 0 DEG C, water and 2M salt is slowly added dropwise
Acid solution, drop are repeatedly extracted after finishing with ethyl acetate, in ethyl acetate containing 8.9 ‰ N- Phenylpyrrolidine, 1.3 ‰
Dimethyl carbonate merges organic phase, is washed with saturated sodium bicarbonate solution, filters, removes under reduced pressure molten after anhydrous magnesium sulfate is dry
Agent obtains light yellow oil, as hydroxytyrosol, and it is 97% that high performance liquid chromatograph, which detects purity, yield 90%.
Comparative example 6 and embodiment 7 are it is found that the available higher target product yield of embodiment 7 and target product
Purity is a kind of preparation method of the hydroxytyrosol of high efficiency, high yield.
Routine operation in operating procedure of the invention is well known to those skilled in the art, herein without repeating.
Technical solution of the present invention is described in detail in embodiment described above, it should be understood that the above is only
For specific embodiments of the present invention, it is not intended to restrict the invention, all any modifications made in spirit of the invention,
Supplement or similar fashion substitution etc., should all be included in the protection scope of the present invention.
Claims (10)
1. preparing the new method of high-purity hydroxytyrosol, it is characterised in that: the synthetic route of the hydroxytyrosol is as follows:
2. the new method of preparation high-purity hydroxytyrosol according to claim 1, it is characterised in that: the new method is specific
The following steps are included:
Step 1: lithium aluminium hydride reduction is put into dry single port bottle, solvent is added, is sufficiently mixed uniform solution, it is spare；
Step 2: being at 0 DEG C to step 1 that 3,4-Dihydroxyphenylacetic acid is added portionwise in solution, remove ice after addition
Bath, makes its reaction；
Step 3: reaction solution after completion of the reaction being placed at 0 DEG C, water and hydrochloric acid solution is slowly added dropwise, drop uses ethyl acetate after finishing
Extraction 2-4 times merges organic phase, is then washed 2-4 times with sodium bicarbonate aqueous solution, then filters and remove after anhydrous magnesium sulfate is dry
Salt, evaporating solvent under reduced pressure, obtaining light yellow oil is hydroxytyrosol.
3. the new method of preparation high-purity hydroxytyrosol according to claim 2, it is characterised in that: used in the step 1
The calcium pantothenate of aluminium chloride and 0.012-0.016% in lithium aluminium hydride reduction containing 0.023-0.025%.
4. the new method of preparation high-purity hydroxytyrosol according to claim 3, it is characterised in that: left in the calcium pantothenate
The mass ratio for revolving calcium pantothenate and dextro calcium pantothenate is 1:90-95.
5. the new method of preparation high-purity hydroxytyrosol according to claim 2, it is characterised in that: used in the step 1
Solvent is benzene or 1,2- dichloroethanes or methylene chloride or 1,4- dioxane or ether or tetrahydrofuran.
6. the new method of preparation high-purity hydroxytyrosol according to claim 2, it is characterised in that: molten in the step 1
Liquid concentration is 1.5-2.0mol/L.
7. it is according to claim 2 preparation high-purity hydroxytyrosol new method, it is characterised in that: the lithium aluminium hydride reduction and
The molar ratio of 3,4- dihydroxyphenyl acetic acid is 4-6:1.
8. the new method of preparation high-purity hydroxytyrosol according to claim 2, it is characterised in that: anti-in the step 2
To answer temperature be 20-100 DEG C, time 2-20h.
9. the new method of preparation high-purity hydroxytyrosol according to claim 2, it is characterised in that: salt in the step 3
The concentration of acid solution is 1.5-2.5M.
10. the new method of preparation high-purity hydroxytyrosol according to claim 2, it is characterised in that: washed in the step 3
The sodium bicarbonate aqueous solution washed is saturated sodium bicarbonate solution.
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| CN110128246A (en) * | 2019-06-10 | 2019-08-16 | 杭州志源生物科技有限公司 | A kind of preparation method of hydroxytyrosol |
| RU2722142C1 (en) * | 2019-09-30 | 2020-05-27 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Новосибирский государственный педагогический университет" | Two-step method of producing hydroxytyrosol from tyrosol |
| CN111499498A (en) * | 2020-04-27 | 2020-08-07 | 江苏惠利生物科技有限公司 | Method for extracting high-purity hydroxytyrosol from fermentation liquor |
| CN114195640A (en) * | 2021-12-27 | 2022-03-18 | 攀枝花学院 | Synthetic process of hydroxytyrosol and intermediate thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110128246A (en) * | 2019-06-10 | 2019-08-16 | 杭州志源生物科技有限公司 | A kind of preparation method of hydroxytyrosol |
| CN110128246B (en) * | 2019-06-10 | 2022-07-26 | 杭州志源生物科技有限公司 | Preparation method of hydroxytyrosol |
| RU2722142C1 (en) * | 2019-09-30 | 2020-05-27 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Новосибирский государственный педагогический университет" | Two-step method of producing hydroxytyrosol from tyrosol |
| CN111499498A (en) * | 2020-04-27 | 2020-08-07 | 江苏惠利生物科技有限公司 | Method for extracting high-purity hydroxytyrosol from fermentation liquor |
| CN114195640A (en) * | 2021-12-27 | 2022-03-18 | 攀枝花学院 | Synthetic process of hydroxytyrosol and intermediate thereof |
| CN114195640B (en) * | 2021-12-27 | 2024-03-12 | 攀枝花学院 | Synthesis process of hydroxytyrosol and intermediate thereof |
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