CN106220601A - A kind of synthetic method of pinocembrin - Google Patents
A kind of synthetic method of pinocembrin Download PDFInfo
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- CN106220601A CN106220601A CN201610575023.4A CN201610575023A CN106220601A CN 106220601 A CN106220601 A CN 106220601A CN 201610575023 A CN201610575023 A CN 201610575023A CN 106220601 A CN106220601 A CN 106220601A
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- Prior art keywords
- pinocembrin
- trihydroxy
- crude product
- acetophenones
- synthetic method
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/32—2,3-Dihydro derivatives, e.g. flavanones
Abstract
The present invention provides the synthetic method of a kind of pinocembrin, comprises the following steps: at ambient temperature, phloroglucinol and acetonitrile is stirred, and adds phosphorous oxychloride reaction, obtains 2,4,6 trihydroxy-acetophenones；Under catalyst L Proline-Catalyzed effect, by the 2 of gained, 4,6 trihydroxy-acetophenones and benzaldehyde occur ring closure reaction to generate pinocembrin crude product in DMF；By the pinocembrin crude product ethyl alcohol recrystallization of gained, use activated carbon decolorizing, obtain pinocembrin.The synthetic method craft of the present invention is simple, low cost, saves the time, and productivity is high, is suitable for industrialized production.
Description
Technical field
The invention belongs to the field of chemical synthesis, be specifically related to the synthetic method of a kind of pinocembrin.
Background technology
Pinocembrin, also known as Sciurus vulgaris element, is a kind of flavanone being present in various plants, and flavanone, also known as flavane
The quilts such as ketone, is the one in flavone compound, is distributed in Rosaceae, Rutaceae, Zingiberaceae, Compositae, Ericaceae, pulse family are planted
In thing.
The structural formula of pinocembrin is as follows:
Flavanone kind composition has many lifes such as sterilization, antiinflammatory, antitumor, anti HIV-1 virus, antimutagenic, antioxidation
Thing activity, is the compound that a class researching value is the highest.Natural flavanone kind composition has hydroxyl, isopentene group, benzyl more
The substituent groups such as epoxide, methoxyl group, geranyl.Additionally, flavanone can reach 10 more than by decorating site so that it is have greatly
Structural modification potentiality.Pinocembrin is present in nut pine, cherry tree, Eucalyptus, the heartwood of willow and propolis, by various colors
Spectrum isolation technics only can get a small amount of sterling.
Chinese patent CN103951644A method quickly preparing pinocembrin has been invented a kind of by extracting system in Radix Glycyrrhizae
The method of standby pinocembrin, but wherein used polyamide isolation technics, relatively costly.So far there are no other about pinocembrin
Synthesis report.Modern pharmacology confirms that pinocembrin has pharmacologically active widely, such as antibacterial, antiinflammatory, antioxidation and anticancer etc., and
Can protect neural from the damage brought because of cerebral ischemia, show that pinocembrin has the latent effect as new drug development precursor.
Summary of the invention
The goal of the invention of the present invention is to provide the synthetic method of a kind of pinocembrin, mainly solves synthesis work in prior art
Skill is loaded down with trivial details, and productivity is low, the problem that cost is high.
Technical scheme: the synthetic method of the pinocembrin provided, comprises the following steps:
Step 12,4, the synthesis of 6 trihydroxy-acetophenones
At ambient temperature, phloroglucinol and acetonitrile are stirred, add phosphorus oxychloride reaction, obtain 2,4,6 trihydroxies
1-Phenylethanone.；
The synthesis of step 2 crude product
Under catalyst L-PROLINE catalytic action, by the 2 of step 1 gained, 4,6 trihydroxy-acetophenones and benzaldehyde at N,
Dinethylformamide (DMF) occur ring closure reaction generate pinocembrin crude product；
Step 3 refines
By the pinocembrin crude product ethyl alcohol recrystallization of step 2 gained, use activated carbon decolorizing, obtain pinocembrin.
Above-mentioned steps 1 is specifically: at ambient temperature, phloroglucinol and acetonitrile is joined and is equipped with magnetic stirring apparatus
There-necked flask stirs, adds phosphorus oxychloride reaction, obtain 2,4,6 trihydroxy-acetophenones；Described phloroglucinol, acetonitrile and oxygen
The mass ratio of phosphorus chloride is 1:0.8-0.86:2.6-3.0.
Above-mentioned steps 2 is specifically: under L-PROLINE catalytic action, reaction temperature is 80 DEG C, by the 2 of step 1 gained, 4,
6 trihydroxy-acetophenones and benzaldehyde join in DMF and react, and generate pinocembrin crude product；Described 2,4,6-trihydroxy-acetophenones, benzene
Formaldehyde, L-PROLINE and DMF mass ratio are 1:0.65-0.8:0.018-0.03:1.6-1.8.
Above-mentioned steps 3 is specifically: be the ethyl alcohol recrystallization of 80% by the pinocembrin crude product mass concentration of step 2 gained,
Use activated carbon decolorizing, obtain pinocembrin；Described pinocembrin crude product, ethanol and and the mass ratio of activated carbon be 1:10-12:
0.12-0.15。
Advantages of the present invention:
The synthetic method craft of the present invention is simple, low cost, saves the time, and productivity is high, is suitable for industrialized production.
Detailed description of the invention
The synthetic route of the present invention is as follows:
Embodiment one
1,2, the preparation of 4,6-trihydroxy-acetophenones
In the 500 milliliters of there-necked flasks being equipped with magnetic force motor stirrer, add anhydrous phloroglucinol 50g, 52 milliliters
Acetonitrile.Start under room temperature and after magnetic stirrer is sufficiently stirred for one hour, start to drip phosphorous oxychloride 52 milliliters, within 2 hours, drip
Finish.Then proceed to stirring, react 6h, stand overnight.Slowly being poured into by reactant liquor in 200 milliliters of water, reflux 2h, adds 2 grams of work
Property charcoal continue backflow 30min, filtered while hot.Filtrate cools down and places 24h, separates out crystallization.Sucking filtration, filtration cakes torrefaction.Obtain yellow pin
Shape product 54g.
2, the synthesis of pinocembrin
By 2,4,6-trihydroxy-acetophenones 54 grams, benzaldehyde 35 grams, 1 gram of L-PROLINE and 100 milliliters of DMF add 500 millis
Rising in three mouthfuls of reaction bulbs, reactant liquor was poured in 500 milliliters of frozen water after 20 hours by 80 DEG C of reactions, sucking filtration after stirring eight hours.Filter
Cake is pinocembrin crude product, weight in wet base 78 grams.
3, refined
Pinocembrin crude product obtained by upper step with 80% ethyl alcohol recrystallization.78 grams of crude products add the second of 800 milliliter 80%
Refluxing one hour in alcohol-water solution, adds 10 grams of activated carbon decolorizings after 30 minutes, filtered while hot removing activated carbon, filtrate decompression is dense
It is reduced to 100ml, places crystallization 24 hours.Sucking filtration, is dried to obtain 98% pinocembrin white crystals 45 grams.
Embodiment two
1,2, the preparation of 4,6-trihydroxy-acetophenones
In the 50 milliliters of there-necked flasks being equipped with magnetic force motor stirrer, add anhydrous phloroglucinol 25g, 26 milliliters of second
Nitrile.Starting under room temperature and start to drip phosphorous oxychloride 26 milliliters after magnetic stirrer is sufficiently stirred for one hour, dropping in 2 hours is complete.
Then proceed to stirring, react 6h, stand overnight.Slowly being poured into by reactant liquor in 100 milliliters of water, reflux 2h, adds 2 grams of activated carbons
Continue backflow 30min, filtered while hot.Filtrate cools down and places 24h, separates out crystallization.Sucking filtration, filtration cakes torrefaction.Obtain yellow needles to produce
Thing 26g.
2, the synthesis of pinocembrin
By 2,4,6-trihydroxy-acetophenones 27 grams, benzaldehyde 18 grams, 0.6 gram of L-PROLINE and 60 milliliters of DMF add 500 millis
Rising in three mouthfuls of reaction bulbs, reactant liquor was poured in 300 milliliters of frozen water after 20 hours by 80 DEG C of reactions, sucking filtration after stirring eight hours.Filter
Cake is pinocembrin crude product, weight in wet base 38 grams.
3, refined
Pinocembrin crude product obtained by upper step with 80% ethyl alcohol recrystallization.38 grams of crude products add the second of 400 milliliter 80%
Refluxing one hour in alcohol-water solution, adds 6 grams of activated carbon decolorizings after 30 minutes, filtered while hot removing activated carbon, filtrate decompression is dense
It is reduced to 50ml, places crystallization 24 hours.Sucking filtration, is dried to obtain 98% pinocembrin white crystals 22 grams.
Embodiment three
1,2, the preparation of 4,6-trihydroxy-acetophenones
In the 500 milliliters of there-necked flasks being equipped with magnetic force motor stirrer, add anhydrous phloroglucinol 38g, 39 milliliters
Acetonitrile.Start under room temperature and after magnetic stirrer is sufficiently stirred for one hour, start to drip phosphorous oxychloride 39 milliliters, within 2 hours, drip
Finish.Then proceed to stirring, react 6h, stand overnight.Slowly being poured into by reactant liquor in 300 milliliters of water, reflux 2h, adds 2 grams of work
Property charcoal continue backflow 30min, filtered while hot.Filtrate cools down and places 24h, separates out crystallization.Sucking filtration, filtration cakes torrefaction.Obtain yellow pin
Shape product 39g.
2, the synthesis of pinocembrin
By 2,4,6-trihydroxy-acetophenones 39 grams, benzaldehyde 27 grams, 0.75 gram of L-PROLINE and 80 milliliters of DMF add 500
Milliliter three mouthfuls of reaction bulbs in, 80 DEG C reaction 20 hours after reactant liquor is poured in 500 milliliters of frozen water, sucking filtration after stirring eight hours.
Filter cake is pinocembrin crude product, weight in wet base 58 grams.
3, refined
Pinocembrin crude product obtained by upper step with 80% ethyl alcohol recrystallization.58 grams of crude products add the second of 600 milliliter 80%
Refluxing one hour in alcohol-water solution, adds 7 grams of activated carbon decolorizings after 30 minutes, filtered while hot removing activated carbon, filtrate decompression is dense
It is reduced to 150ml, places crystallization 24 hours.Sucking filtration, is dried to obtain 98% pinocembrin white crystals 36 grams.
Embodiment four
1,2, the preparation of 4,6-trihydroxy-acetophenones
In the 500 milliliters of there-necked flasks being equipped with magnetic force motor stirrer, add anhydrous phloroglucinol 10g, 11 milliliters
Acetonitrile.Start under room temperature and after magnetic stirrer is sufficiently stirred for one hour, start to drip phosphorous oxychloride 11 milliliters, within 2 hours, drip
Finish.Then proceed to stirring, react 6h, stand overnight.Slowly being poured into by reactant liquor in 40 milliliters of water, reflux 2h, adds 2 grams of activity
Charcoal continues backflow 30min, filtered while hot.Filtrate cools down and places 24h, separates out crystallization.Sucking filtration, filtration cakes torrefaction.Obtain yellow needles
Product 10g.
2, the synthesis of pinocembrin
By 2,4,6-trihydroxy-acetophenones 10 grams, benzaldehyde 7 grams, 0.2 gram of L-PROLINE and 20 milliliters of DMF add 100 millis
Rising in three mouthfuls of reaction bulbs, reactant liquor was poured in 100 milliliters of frozen water after 20 hours by 80 DEG C of reactions, sucking filtration after stirring eight hours.Filter
Cake is pinocembrin crude product, weight in wet base 15 grams.
3, refined
Pinocembrin crude product obtained by upper step with 80% ethyl alcohol recrystallization.15 grams of crude products add the second of 160 milliliter 80%
Refluxing one hour in alcohol-water solution, adds 10 grams of activated carbon decolorizings after 30 minutes, filtered while hot removing activated carbon, filtrate decompression is dense
It is reduced to 20ml, places crystallization 24 hours.Sucking filtration, is dried to obtain 98% pinocembrin white crystals 8.5 grams.
Embodiment five
1,2, the preparation of 4,6-trihydroxy-acetophenones
In the 1000 milliliters of there-necked flasks being equipped with magnetic force motor stirrer, add anhydrous phloroglucinol 100g, 110 millis
Rise acetonitrile.Start under room temperature and after magnetic stirrer is sufficiently stirred for one hour, start to drip phosphorous oxychloride 104 milliliters, dropping in 2 hours
Complete.Then proceed to stirring, react 6h, stand overnight.Slowly being poured into by reactant liquor in 400 milliliters of water, reflux 2h, adds 2 grams
Activated carbon continues backflow 30min, filtered while hot.Filtrate cools down and places 24h, separates out crystallization.Sucking filtration, filtration cakes torrefaction.Obtain yellow
Needle-like product 108g.
2, the synthesis of pinocembrin
By 2,4,6-trihydroxy-acetophenones 108 grams, benzaldehyde 70 grams, 2 grams of L-PROLINEs and 200 milliliters of DMF add 500 millis
Rising in three mouthfuls of reaction bulbs, reactant liquor was poured in 1000 milliliters of frozen water after 20 hours by 80 DEG C of reactions, sucking filtration after stirring eight hours.Filter
Cake is pinocembrin crude product, weight in wet base 155 grams.
3, refined
Pinocembrin crude product obtained by upper step with 80% ethyl alcohol recrystallization.155 grams of crude products add 1400 milliliter 80%
Ethanol water refluxes one hour, adds 20 grams of activated carbon decolorizings after 30 minutes, filtered while hot removing activated carbon, filtrate decompression
It is concentrated into 200ml, places crystallization 24 hours.Sucking filtration, is dried to obtain 98% pinocembrin white crystals 90 grams.
Through the checking of above-mentioned experiment, the production technology of this synthetic method is fairly simple, and whole technique has only to less than one
Time-of-week, productivity ratio is higher, and the raw material of use is convenient source, is relatively suitable for producing in enormous quantities.
Claims (4)
1. the synthetic method of a pinocembrin, it is characterised in that comprise the following steps:
Step 12,4, the synthesis of 6 trihydroxy-acetophenones
At ambient temperature, phloroglucinol and acetonitrile are stirred, add phosphorous oxychloride reaction, obtain 2,4,6 trihydroxy benzene second
Ketone；
The synthesis of step 2 crude product
Under catalyst L-PROLINE catalytic action, by the 2 of step 1 gained, 4,6 trihydroxy-acetophenones and benzaldehyde in DMF
Ring closure reaction is occurred to generate pinocembrin crude product；
Step 3 refines
By the pinocembrin crude product ethyl alcohol recrystallization of step 2 gained, use activated carbon decolorizing, obtain pinocembrin.
The synthetic method of pinocembrin the most according to claim 1, it is characterised in that described step 1 specifically: at room temperature bar
Under part, join to be equipped with in the there-necked flask of magnetic stirring apparatus by phloroglucinol and acetonitrile and stir, add phosphorous oxychloride
Reaction, obtains 2,4,6 trihydroxy-acetophenones；The mass ratio 1:0.8-0.86:1.7-of described phloroglucinol, acetonitrile and phosphorous oxychloride
1.8。
The synthetic method of pinocembrin the most according to claim 1, it is characterised in that described step 2 specifically: at L-dried meat ammonia
Under acid catalysis, reaction temperature is 80 DEG C, the 2 of step 1 gained, 4,6 trihydroxy-acetophenones and benzaldehyde is joined in DMF
Reaction, generates pinocembrin crude product；Described 2,4,6-trihydroxy-acetophenones, benzaldehyde, L-PROLINE and DMF mass ratio are 1:
0.65-0.8:0.018-0.03:1.7-2.5。
The synthetic method of pinocembrin the most according to claim 1, it is characterised in that described step 3 specifically: by step 2
The pinocembrin crude product mass concentration of gained is the ethyl alcohol recrystallization of 80%, uses activated carbon decolorizing, obtains pinocembrin；Described Qiao
Pine element crude product, ethanol and and the mass ratio of activated carbon be 1:10-12:0.12-0.15.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501226A (en) * | 2017-09-11 | 2017-12-22 | 南昌大学 | A kind of preparation method of 5,7 dihydroxy flavanones |
| CN109553644A (en) * | 2018-11-30 | 2019-04-02 | 陕西嘉禾生物科技股份有限公司 | A kind of preparation method of acacetin |
| CN115850225A (en) * | 2022-11-30 | 2023-03-28 | 三原润禾生物科技有限公司 | Application of hesperidin and method for semi-synthesizing chrysin by using hesperidin derivative |
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| WO2014153000A1 (en) * | 2013-03-14 | 2014-09-25 | Chromocell Corporation | Compounds, compositions, and methods for modulating sweet taste |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501226A (en) * | 2017-09-11 | 2017-12-22 | 南昌大学 | A kind of preparation method of 5,7 dihydroxy flavanones |
| CN107501226B (en) * | 2017-09-11 | 2019-08-06 | 南昌大学 | A kind of preparation method of 5,7- dihydroxy flavanones |
| CN109553644A (en) * | 2018-11-30 | 2019-04-02 | 陕西嘉禾生物科技股份有限公司 | A kind of preparation method of acacetin |
| CN115850225A (en) * | 2022-11-30 | 2023-03-28 | 三原润禾生物科技有限公司 | Application of hesperidin and method for semi-synthesizing chrysin by using hesperidin derivative |
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