CN100360489C - Method for synthesizing veratric alcohol - Google Patents
Method for synthesizing veratric alcohol Download PDFInfo
- Publication number
- CN100360489C CN100360489C CNB2006100370593A CN200610037059A CN100360489C CN 100360489 C CN100360489 C CN 100360489C CN B2006100370593 A CNB2006100370593 A CN B2006100370593A CN 200610037059 A CN200610037059 A CN 200610037059A CN 100360489 C CN100360489 C CN 100360489C
- Authority
- CN
- China
- Prior art keywords
- reaction
- synthetic method
- hour
- anhydrous
- temperature
- 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.)
- Expired - Fee Related
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method for resveratrol, including (1) discharging hydrogen bromide gas to benzene solution of p-methoxy benzyl alcohol to obtain p-methoxy benzyl bromide, (2) carrying out reaction of p-benzyl bromide with triethyl phosphate to obtain diethyl p-methoxy benzyl phosphate, (3) carrying out reaction of diethyl p-methoxy benzyl phosphate with sodium amide and 3,5-dimethoxybenzaldehyde to obtain (E)-3, 4', 5-trimethoxystilbene, and (4) carrying out reaction of (E)-3, 4', 5- trimethoxystilbene with aluminum iodide to obtain the final product. The invention has the advantages of raw materials easy to get, lowered cost, mild reaction conditions, simplified operation, and enhanced yield.
Description
Technical field
The present invention relates to the synthetic method of functional food ingredient trans-resveratrol.
Technical background
Compound trans-resveratrol (Resveratrol) chemistry (E)-3 by name, 4 ', 5-trihydroxy-toluylene, it is a kind of non-flavonoid polyphenolic substance that contains the stilbene class formation, effect with significantly anti-oxidant, Green Tea Extract and the aging of delaying human body function, pharmacologically active with anticancer significantly, anti-inflammatory, sterilization, reducing blood-fat, antithrombotic, atherosclerosis, prevention cardiovascular and cerebrovascular diseases, can be widely used in fields such as healthcare products, medicine, makeup, in food applications, can be used as functional food ingredient.The structure of this compound is as follows:
The synthetic method of bibliographical information mainly contains Wittig method and Heck method.Wittig method reaction conditions is relatively harsher, relatively stricter to temperature and anhydrous requirement, in preparation (E)-3,4 ', during 5-trimethoxy toluylene, by product is not soluble in water, make troubles to product purification, and products therefrom is the cis-trans mixture separation method complexity, need further isomerization, transformation ratio is difficulty.Heck method advantage is the stereoselectivity height, and reactions steps is less, but the raw material that uses is difficult for preparation, and used catalyzer is the complex compound that contains palladium, cost an arm and a leg and toxicity big.
Have bibliographical information (40 (5): synthetic method 1130-1136) is as follows for Mohammad Ahad Ali, Chem.Pharm.Bull.1992:
The document is to adopt the wittig reaction, has certain drawback: reaction conditions is relatively harsher, and temperature of reaction is lower, and requires anhydrous condition; During preparation product II, the by product of generation is not soluble in water, brings difficulty to product purification, comes purifying with column chromatography method, causes a large amount of wastes of solvent and product; During preparation product III, get the cis-trans mixtures II earlier, need further isomerization, and transformation ratio is difficult; Adopt BB3 deprotection base, amount ratio is bigger, and the price comparison costliness, to light, heat and water unstable, inconvenient operation.
Summary of the invention
The purpose of this invention is to provide a kind of method of the Wittig-Horner of utilization reaction synthesizing resveratrol, desired raw material is easy to get, and has reduced cost, the reaction conditions gentleness, and operation obtains simplifying, and productive rate also is improved.
Synthetic route of the present invention:
The synthetic method of trans-resveratrol provided by the invention comprises with following steps:
A: it is the benzole soln of the p-methoxybenzyl alcohol of 0.2～0.3g/ml that HBr gas is fed concentration, makes solution by muddy bleach, 50-60 ℃ of reaction 0.5-1 hour, removes benzene solvent, makes 4-methoxybenzyl bromide;
B: gained 4-methoxybenzyl bromide and triethyl-phosphite with the mixed of 20g: 55～60ml after under 80-100 ℃ of condition the reaction 2-3 hour, make the methoxy-benzyl diethyl phosphoric acid;
C: gained is to methoxy-benzyl diethyl phosphoric acid and sodium methylate, 3, the 5-dimethoxy benzaldehyde is with 35～40: 23～26: 23～26 mass ratio reacted 6-8 hour after mixing at ambient temperature, impouring frozen water miscellany, again through ethyl acetate extraction, concentrate, use the alcohol-water recrystallization then, get white plates crystal (E)-3,4 ', 5-trimethoxy toluylene;
D:(E)-3,4 ', 5-trimethoxy toluylene and AlI
3With 3～5: 14～16 mass ratio mixed the back in 50-70 ℃ of conditioned response 3-5 hour, and demethylating gets white mass, i.e. trans-resveratrol.
Wherein the temperature of reaction in the steps A is preferred 58 ℃, preferred 0.5 hour of reaction times; After the reaction product washing, the anhydrous MgSO of organic phase
4Drying, rotary evaporation is to remove benzene.Remove benzene solvent gained 4-methoxybenzyl bromide and need not purifying and promptly can be used for the next step, to not influence of final product.
Reaction need not solubilizing agent among the step B, and the preferred 90-100 of temperature of reaction ℃, preferred 3 hours of reaction times.
The preferred 20-30 of temperature of reaction among the step C ℃, preferred 7 hours of reaction times.
The preferred 52-58 of temperature of reaction among the step D ℃, preferred 4 hours of reaction times.AlI3 can make at reaction scene in acetonitrile with aluminium foil and iodine, the preparation method is as follows: add in the dry round bottom piece bottle of taking back stream prolong and drying tube and use the washed aluminium foil fragment of dilute hydrochloric acid, dehydrated alcohol, anhydrous diethyl ether and anhydrous acetonitrile in advance successively, crystal iodine and the anhydrous second eyeball of handling through P205, three's amount ratio is 2.4g: 14g: 40ml, elder generation's ice bath stirring reaction, the mild back of question response back flow reaction to the iodine color fade promptly.
The present invention has remarkable advantages than literature method: carry out bromination with HBr, and the reaction conditions gentleness, aftertreatment obtains simplifying, and need not to be further purified; Adopt phosphatide to replace microcosmic salt, its by product is soluble in water, helps the purifying of target product, need not post; Adopt AlI
3The deprotection base is than BBr
3, cost is reduced, and operation obtains simplifying.In a word, method reaction conditions gentleness provided by the invention, operation obtains simplifying, and productive rate also is improved, thereby makes the synthesis technique of trans-resveratrol be easier to industrialization.
Embodiment
Embodiment one:
Steps A: get the 20g p-methoxybenzyl alcohol, benzene 100ml stirs water-bath in three mouthfuls of round-bottomed flasks that prolong is housed, evenly fast feed HBr gas, solution is got final product by muddy bleach, reheat to 58 ℃, reacted washing 300ml * 4, the anhydrous MgSO of organic phase about 0.5 hour
4Drying, rotary evaporation is removed benzene, gets yellow oily 4-methoxybenzyl bromide 20.81g (yield 71.4%), is directly used in next step reaction.
Step B:19.75g 4-methoxybenzyl bromide (not purification process) reacts 3h with the 56ml triethyl-phosphite under 90-100 ℃ of condition, triethyl-phosphite is removed in the rotation decompression, must be directly used in next step reaction to methoxy-benzyl diethyl phosphoric acid 36.98g.
In the dry DMF of 250ml, ice bath is cooled to below 0 ℃ step C:36.98g, stirs fast, adds 24.55gNaOCH to methoxy-benzyl diethyl phosphoric acid (not purification process)
3, stir about half an hour, make to add NaOCH
3Homodisperse; Slowly drip 25.16g3, the dry DMF solution 50ml of 5-dimethoxy benzaldehyde drips nature and is warmed up to room temperature and then reacts 7h.Reaction solution is poured in the 1700ml frozen water, stirs, and drips rare HCl neutralization, promptly has solid to separate out, and it is limpid that liquid becomes, filter yellowish solid, use the alcohol-water recrystallization, (E)-3,4 ', 5-trimethoxy toluylene 13.5g (two go on foot total recovery 50.9%).
Step D: in the dry round bottom piece bottle of taking back stream prolong and drying tube, add 2.4g aluminium foil fragment (in advance successively with dilute hydrochloric acid, dehydrated alcohol, anhydrous diethyl ether and anhydrous acetonitrile washing), crystal iodine 14g and the anhydrous second eyeball of 40ml (through P
2O
5Handle), first ice bath stirring reaction, the mild back of question response back flow reaction is to iodine color fade (about 1h).To freshly prepd AlI
3Slowly drip 4g (E)-3 in the suspension, 4 ', the anhydrous second eyeball solution 20ml (about 30min) of 5-trimethoxy toluylene, 55 ℃ were reacted about 4 hours.The second eyeball is removed in decompression, and water-bath drips the 30ml frozen water, and with ethyl acetate extraction 50ml * 3, decompression is removed ethyl acetate and got brown solid, uses the ethanol/water mixed solvent recrystallization, gets pale solid trans-resveratrol 1.16g (yield 34%).
Embodiment two:
Steps A: get the 20g p-methoxybenzyl alcohol, benzene 100ml stirs water-bath in three mouthfuls of round-bottomed flasks that prolong is housed, evenly fast feed HBr gas, solution is got final product by muddy bleach, reheat to 50 ℃, reacted washing 300ml * 4, the anhydrous MgSO of organic phase about 1 hour
4Drying, rotary evaporation is removed benzene, gets the yellow oily 4-methoxybenzyl bromide, is directly used in next step reaction.
Step B:19.75g 4-methoxybenzyl bromide (not purification process) reacts 2h with the 56ml triethyl-phosphite under 90-100 ℃ of condition, triethyl-phosphite is removed in the rotation decompression, must be directly used in next step reaction to methoxy-benzyl diethyl phosphoric acid 35.08g.
In the dry DMF of 250ml, ice bath is cooled to below 0 ℃ step C:36.98g, stirs fast, adds 24.55gNaOCH to methoxy-benzyl diethyl phosphoric acid (not purification process)
3, stir about half an hour, make to add NaOCH
3Homodisperse; Slowly drip 25.16g3, the dry DMF solution 50ml of 5-dimethoxy benzaldehyde drips nature and is warmed up to room temperature and then reacts 6h.Reaction solution is poured in the 2000ml frozen water, stirs, and drips rare HCl neutralization, promptly has solid to separate out, and it is limpid that liquid becomes, filter yellowish solid, use the alcohol-water recrystallization, (E)-3,4 ', 5-trimethoxy toluylene 12.6g (two go on foot total recovery 47.5%).
Step D: in the dry round bottom piece bottle of taking back stream prolong and drying tube, add 2.4g aluminium foil fragment (in advance successively with dilute hydrochloric acid, dehydrated alcohol, anhydrous diethyl ether and anhydrous acetonitrile washing), crystal iodine 14g and the anhydrous second eyeball of 40ml (through P
2O
5Handle), first ice bath stirring reaction, the mild back of question response back flow reaction is to iodine color fade (about 1h).To freshly prepd AlI
3Slowly drip 4g (E)-3 in the suspension, 4 ', the anhydrous second eyeball solution 20ml (about 30min) of 5-trimethoxy toluylene, 65 ℃ were reacted about 3.5 hours.The second eyeball is removed in decompression, and water-bath drips the 30ml frozen water, and with ethyl acetate extraction 50ml * 3, decompression is removed ethyl acetate and got brown solid, uses the ethanol/water mixed solvent recrystallization, gets pale solid trans-resveratrol 1.06g (yield 31%).
Claims (7)
1, a kind of synthetic method of trans-resveratrol is characterized in that in turn including the following steps:
A: it is the benzole soln of the p-methoxybenzyl alcohol of 0.2～0.3g/ml that HBr gas is fed concentration, makes solution by muddy bleach, 50-60 ℃ of reaction 0.5-1 hour, removes benzene solvent, makes 4-methoxybenzyl bromide;
B: gained 4-methoxybenzyl bromide and triethyl-phosphite with the mixed of 20g: 55～60ml after under 80-100 ℃ of condition the reaction 2-3 hour, make the methoxy-benzyl diethyl phosphoric acid;
C: gained is to methoxy-benzyl diethyl phosphoric acid and sodium methylate, 3, the 5-dimethoxy benzaldehyde is with 35～40: 23～26: 23～26 mass ratio reacted 6-8 hour after mixing at ambient temperature, impouring frozen water miscellany, again through ethyl acetate extraction, concentrate, use the alcohol-water recrystallization then, get white plates crystal (E)-3,4 ', 5-trimethoxy toluylene;
D: gained (E)-3,4 ', 5-trimethoxy toluylene and AlI
3Mass ratio by 3～5: 14～16 mixed the back in 50-70 ℃ of conditioned response 3-5 hour, and demethylating gets white mass, i.e. trans-resveratrol.
2, synthetic method according to claim 1 is characterized in that: the temperature of reaction in the described steps A is 58 ℃, and the reaction times is 0.5 hour; After the reaction product washing, the anhydrous MgSO of organic phase
4Drying, rotary evaporation is to remove benzene.
3, synthetic method according to claim 1 is characterized in that: temperature of reaction is 90-100 ℃ among the described step B, and the reaction times is 3 hours.
4, synthetic method according to claim 1 is characterized in that: the temperature of reaction among the described step C is 20-30 ℃, and the reaction times is 7 hours.
5, synthetic method according to claim 1 is characterized in that: the temperature of reaction among the described step D is 52-58 ℃, and the reaction times is 4 hours.
6, synthetic method according to claim 1 is characterized in that: AlI
3Reaction scene in acetonitrile makes by aluminium foil and iodine.
7, synthetic method according to claim 6 is characterized in that described AlI
3Make by following method scene: in the dry round bottom piece bottle of taking back stream prolong and drying tube, add and use the washed aluminium foil fragment of dilute hydrochloric acid, dehydrated alcohol, anhydrous diethyl ether and anhydrous acetonitrile in advance successively, crystal iodine and through P
2O
5The anhydrous second eyeball of handling, three's amount ratio is 2.4g: 14g: 40ml, first ice bath stirring reaction, the mild back of question response back flow reaction is to the iodine color fade promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100370593A CN100360489C (en) | 2006-08-16 | 2006-08-16 | Method for synthesizing veratric alcohol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100370593A CN100360489C (en) | 2006-08-16 | 2006-08-16 | Method for synthesizing veratric alcohol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1907931A CN1907931A (en) | 2007-02-07 |
| CN100360489C true CN100360489C (en) | 2008-01-09 |
Family
ID=37699188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100370593A Expired - Fee Related CN100360489C (en) | 2006-08-16 | 2006-08-16 | Method for synthesizing veratric alcohol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100360489C (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102050702B (en) * | 2010-12-10 | 2013-03-27 | 蒋勇 | Method for promoting synthesis of resveratrol by micro waves |
| CN102050704A (en) * | 2011-01-04 | 2011-05-11 | 暨南大学 | Method for preparing resveratrol |
| CN104326880A (en) * | 2014-10-17 | 2015-02-04 | 西安莹朴生物科技股份有限公司 | Resveratrol synthesis preparation method |
| CN105237567B (en) * | 2015-11-09 | 2017-09-29 | 河北工业大学 | A kind of preparation method containing fragrant methyl phosphonate |
| CN108689805B (en) * | 2018-05-22 | 2021-08-03 | 荆楚理工学院 | Preparation method of resveratrol |
| CN109970517B (en) * | 2019-04-28 | 2021-09-17 | 杭州师范大学 | Preparation method of resveratrol compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1466884A1 (en) * | 2003-04-08 | 2004-10-13 | Sochinaz SA | Process for the preparation of resveratrol and its uses |
-
2006
- 2006-08-16 CN CNB2006100370593A patent/CN100360489C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1466884A1 (en) * | 2003-04-08 | 2004-10-13 | Sochinaz SA | Process for the preparation of resveratrol and its uses |
Non-Patent Citations (5)
| Title |
|---|
| 天然产物白藜芦醇的合成. 白冬花等人.天津师范大学学报（自然科学版），第26卷第1期. 2006 * |
| 白藜芦醇合成研究. 李晓光等人.中国食品添加剂，第5期. 2002 * |
| 白藜芦醇的化学合成研究. 王世盛等人.中国药物化学杂志，第14卷第2期. 2004 * |
| 白藜芦醇的合成. 王尊元等人.中国医药工业杂志，第34卷第9期. 2003 * |
| 白藜芦醇的药理活性及制备方法. 郑乾刚等人.化学试剂，第28卷第2期. 2006 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1907931A (en) | 2007-02-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100360489C (en) | Method for synthesizing veratric alcohol | |
| CN103739448B (en) | The method being prepared high-purity borneol by Camphora and reduzate thereof, Borneolum Syntheticum | |
| CN102911022A (en) | Method for artificially synthesizing natural curcumin compound | |
| EP2760444A1 (en) | Cannabinoid carboxylic acids, salts of cannabinoid carboxylic acids, and the production and uses of same | |
| Kornblum et al. | The conversion of nitriles to amides and esters to acids by the action of sodium superoxide | |
| CN101768073A (en) | Method for preparing ferulic acid from Chinese angelica | |
| CN104744230A (en) | Method for synthesizing vitamin K1 | |
| CN114105738B (en) | Method for synthesizing alkyl alkenyl ether by photocatalysis | |
| CN112441952B (en) | Cannabidiol-3-sulfonic acid, preparation method and application thereof, and cannabidiol derivative | |
| CN102712565B (en) | Acylations in micro reaction systems | |
| JPS5920655B2 (en) | Manufacturing method for new naphthalene derivatives | |
| CN103319316B (en) | Green preparation method of dihydroxy dibutyl ether | |
| WO2016119270A1 (en) | Method of preparing high-purity borneol from camphor, camphor reduction product, and borneo camphor | |
| CN105399615A (en) | Method for synthesizing vitamin K1 | |
| CN103450130A (en) | Toluylene compound and preparation method thereof | |
| CN104961716B (en) | Method for separating high-purity lactone type lovastatin from fermentum rubrum powder | |
| CN103980481B (en) | The preparation method of watermiscible vitamin E | |
| CN103102264B (en) | Preparation method of salicylic acid compound | |
| CN105418381A (en) | Oxyresveratrol synthesis method | |
| CN103172499B (en) | Oxyresveratrol synthesis method | |
| CN102127044A (en) | Method for synthesizing 5,7-dihydroxy flavone | |
| CN104909994A (en) | Method for synthesizing ciprofibrate intermediate and the intermediate | |
| CN102010323B (en) | Method for synthesizing ibuprofen and analogues thereof | |
| CN104803895B (en) | A kind of method for preparing sulfinic acid ester as raw material with benzenesulfonylmethyl isonitrile | |
| CN105085460B (en) | A kind of preparation method of 4 phenyl coumarin class compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080109 Termination date: 20100816 |