CN107698434A - A kind of synthesis technique of Rhein - Google Patents
A kind of synthesis technique of Rhein Download PDFInfo
- Publication number
- CN107698434A CN107698434A CN201610644506.5A CN201610644506A CN107698434A CN 107698434 A CN107698434 A CN 107698434A CN 201610644506 A CN201610644506 A CN 201610644506A CN 107698434 A CN107698434 A CN 107698434A
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- China
- Prior art keywords
- rhein
- butadiene
- methoxyl group
- juglone
- dissolved
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/093—Preparation of carboxylic acids or their salts, halides or anhydrides by hydrolysis of —CX3 groups, X being halogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a kind of fully synthetic technique of Rhein, and juglone and the butadiene of 3 M 1 (methoxyl group) 1,3 are obtained into mixture through diene synthesis, and Rhein is hydrolyzed to obtain after refined.
Description
Technical field
The present invention relates to a kind of synthesis technique of compound.
Background technology
Rheum officinale is polygonaceae Polygonum herbaceos perennial, is a kind of conventional Chinese medicine, and medicinal part is root and rhizome.China four
River the north and Gansu are the major production bases of Rheum officinale.Rheum officinale first recorded in《Sheng Nong's herbal classic》, on the books " main lower extravasated blood,
Blood closes, fever and chills, broken a lump in the abdomen causing distension and pain, stays drink place food, cleanses stomach, pushes away Chen Zhixin, tonneau trough, helping digestion, peace and the five internal organs in tune ".
Recent decades, the clinical research of rheum officinale achieve breakthrough progress, and rheum officinale goes out in the acute Stomach duodenum for the treatment of
Blood, peptic ulcer, acute pancreatitis, disease of biliary tract (such as acute cholecystitis, cholelithiasis, ascariasis of biliary tract, hematobilia),
The illnesss such as acute viral hepatitis, hyperbilirubinemia, chronic renal failure, hyperlipidemia, obesity, mass formed by blood stasis all embody
The effect of unique.Wherein research finds that Main Ingredients and Appearance anthraquinone compounds are imitated in treatment leukaemia and suppression tumour cell in rheum officinale
Fruit is notable, and domestic and foreign scholars start to pay close attention to again.
Main active chemical Rhein, Chrysophanol, the rheum emodin of rheum officinale, Rhein have antitumor, anti-inflammatory, resisted
The effects such as bacterium, drop blood ester and regulation renal function.Discovered in recent years in treating diabetic nephropathy embody uniqueness the effect of.Rheum officinale
Acid is widely distributed in plant kingdom, but content is relatively low, and anthraquinone total content only has 3% -5% in rheum officinale, and extracted amount is less, cost compared with
It is high.Chemically synthesis Rhein has preferable market efficiency, is also beneficial to environmental protection and product quality.
The synthesis of Rhein at present has semi-synthetic and fully synthetic two kinds of modes.Semi-synthesizing technology rely on natural resources, it is necessary to
Substantial amounts of plant resources is consumed, there is limitation.Such as Chinese invention patent（Application number 201110200055.3,
201310657900.9）It is that triacetyl aloe-emodin is made through acetylation in raw material to disclose from aloe Rhein, then through chromium
Diacerein is made in oxidation, the synthesis technique of the semi-synthetic Rhein of last deacetylated synthesis Rhein；Such as《Sichuan chemical industry and corruption
Erosion control》The 1-2 pages of the fifth phase in 2001 is disclosed using rheum officinale as raw material, it is extracted go out Chrysophanol, through acetylation process, then oxygen
It is melted into diacerein, the synthesis technique of the semi-synthetic Rhein of last deacetylated synthesis Rhein.
It is fully synthetic relative to semi-synthetic because there is advantage independent of natural resources, such as Chinese invention patent（Application number
200410103346.0、200610106762.5）Disclose using 3- nitrophthalic acids acid anhydride and ask cresols as initiation material,
Intermediate Chrysophanol is prepared through Fu Ke acylation reactions, iron powder reducing reaction, diazo-reaction, hydrolysis, cyclization, then through second
Acylated processing, is reoxidised into diacerein, the fully synthetic technique of the semi-synthetic Rhein of last deacetylated synthesis Rhein；As extensively
Eastern pharmaceutical college Zhang Dezhi master's thesis《The chemical composition of rheum officinale and this study on the synthesis of active ingredient Rhein》It is open
Prepare with Micheal addition reactions the fully synthetic technique of Rhein.Fully synthetic technique is in laboratory stage at present, also
Do not have the production of industrialization, this is mainly relevant with fully synthetic technological feasibility at present, such as with 3- nitrophthalic acids acid anhydride with
The problem of metacresol exists for the fully synthetic technique of initiation material：（1）For Friedel-Crafts reaction using metacresol as solvent, product separation is relatively tired
It is difficult；（2）Diazotising product poorly water-soluble, is easily separated out in diazo process, influences diazotising effect and yield, hydrolysate matter
Amount is whard to control.
Therefore, there is an urgent need to develop a kind of new, capable of being industrialized fully synthetic technique of Rhein.
The content of the invention
It is an object of the invention to provide a kind of fully synthetic technique of new Rhein.
Synthesis technique disclosed by the invention is that juglone must mix with 3-M-1- (methoxyl group) -1,3- butadiene through diene synthesis
Compound, Rhein is hydrolyzed to obtain after isomers through refined, wherein M is selected from-CN ,-CF3、-CCl3。
Juglone considers to be prepared for raw material by 1,5- bisnaphthols, and 3-M-1- (methoxyl group) -1,3-butadiene is by the chloro- 1- of 3-
(methoxyl group) -1,3- butadiene is Material synthesis, and wherein M is selected from-CN,-CF3、-CCl3。
The fully synthetic technique of Rhein of the present invention comprises the following steps that：
（1）Take 3-M-1- (methoxyl group) -1,3-butadiene to be dissolved in toluene liquid, add juglone, be heated to reflux, first is evaporated in vacuo
Benzene, products therefrom are crystallized with petroleum ether, remove isomers.
（2）Above-mentioned petroleum ether crystallized product is dissolved in hydrochloride ethanol liquid, is heated to reflux, and cold filtration obtains crude product, crude product
Add alkali soluble solution, after filtering, acid adding separates out.
Preferably fully synthetic technique comprises the following steps that Rhein of the present invention：
Take 3-M-1- (methoxyl group) -1,3-butadiene to be dissolved in toluene liquid, add juglone, under nitrogen protection, be slowly heated to back
Stream, after flowing back 12 hours, toluene is evaporated in vacuo.Products therefrom is crystallized with petroleum ether, removes isomers.
Above-mentioned petroleum ether crystallized product is dissolved in 30% hydrochloride ethanol liquid, is heated to reflux 10 hours, cold filtration obtains slightly
Product, crude product adds alkali soluble solution, and after filtering, acid adding separates out.
Embodiment
The following examples are used only for that the present invention is explained further, without limiting the scope of the present invention.
Embodiment 1
3- cyano group -1- (methoxyl group) -1,3- butadiene is Material synthesis by 3- chloro- 1- (methoxyl group) -1,3- butadiene.
Take the chloro- butadiene of 1- methoxyl groups -3- to be dissolved in ethanol solution, at 10-20 DEG C, stir the cyaniding of lower dropwise addition 15%
Sodium water solution（Cymag mole is 1.01, and Cymag is slightly excessive）, ethanol is evaporated in vacuo, is extracted with toluene, extract is with anhydrous
It is stand-by after sodium sulphate is dried.
Embodiment 2
Take 3- cyano group -1- (methoxyl group) -1,3-butadiene to be dissolved in toluene liquid, add juglone, under nitrogen protection, be slowly heated to
Backflow, after flowing back 12 hours, toluene is evaporated in vacuo.Products therefrom is crystallized with petroleum ether, removes isomers.Crystallized product is dissolved in
In 30% hydrochloride ethanol liquid, it is heated to reflux 10 hours, cold filtration obtains crude product, and crude product adds alkali soluble solution, and after filtering, acid adding separates out,
Rhein yield is up to 52%.
Embodiment 3
Take 3- trichloromethyls -1- (methoxyl group) -1,3-butadiene to be dissolved in toluene liquid, add juglone, under nitrogen protection, slowly add
After flowing back 12 hours, toluene is evaporated in vacuo to flowing back in heat.Products therefrom is crystallized with petroleum ether, removes isomers.Crystallized product is molten
Solution is heated to reflux 10 hours in 30% hydrochloride ethanol liquid, and cold filtration obtains crude product, and crude product adds alkali soluble solution, after filtering, acid adding
Separate out, Rhein yield is up to 60%.
Claims (1)
1. the fully synthetic technique of a kind of Rhein, it is characterised in that juglone is with 3-M-1- (methoxyl group) -1,3-butadiene through double
Alkene synthesizes to obtain mixture, hydrolyzes to obtain Rhein after refined, its processing step is as follows：
（1）Take 3-M-1- (methoxyl group) -1,3-butadiene to be dissolved in toluene liquid, add juglone, be heated to reflux, first is evaporated in vacuo
Benzene, products therefrom are crystallized with petroleum ether, remove isomers；
M：-CN、CF3、-CCl3
R：-CH3、-C2H5
（2）Above-mentioned petroleum ether crystallized product is dissolved in hydrochloride ethanol liquid, is heated to reflux, and cold filtration obtains crude product, and crude product adds alkali
Dissolving, after filtering, acid adding separates out, and reaction equation is as follows：
。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201610644506.5A CN107698434A (en) | 2016-08-09 | 2016-08-09 | A kind of synthesis technique of Rhein |
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| CN201610644506.5A CN107698434A (en) | 2016-08-09 | 2016-08-09 | A kind of synthesis technique of Rhein |
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| CN107698434A true CN107698434A (en) | 2018-02-16 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5555132A (en) * | 1978-10-18 | 1980-04-22 | Kawasaki Kasei Chem Ltd | Preparation of 2,3-dihydroxy-1,4-naphthoquinone |
| CN1079732A (en) * | 1992-02-28 | 1993-12-22 | 利利工业公司 | Medical compounds |
| WO1997016404A1 (en) * | 1995-11-02 | 1997-05-09 | Girex | Method for preparing substituted anthraquinones and use thereof for preparing rheins |
| CN1216035A (en) * | 1997-02-03 | 1999-05-05 | 吉雷克斯股份有限公司 | Method for preparing substd. anthraguinone and application to preparation of rheins |
| CN1907936A (en) * | 2004-12-19 | 2007-02-07 | 南京莱因医药科技有限公司 | Synthesis method of rhein and Diacerein |
-
2016
- 2016-08-09 CN CN201610644506.5A patent/CN107698434A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5555132A (en) * | 1978-10-18 | 1980-04-22 | Kawasaki Kasei Chem Ltd | Preparation of 2,3-dihydroxy-1,4-naphthoquinone |
| CN1079732A (en) * | 1992-02-28 | 1993-12-22 | 利利工业公司 | Medical compounds |
| WO1997016404A1 (en) * | 1995-11-02 | 1997-05-09 | Girex | Method for preparing substituted anthraquinones and use thereof for preparing rheins |
| CN1216035A (en) * | 1997-02-03 | 1999-05-05 | 吉雷克斯股份有限公司 | Method for preparing substd. anthraguinone and application to preparation of rheins |
| CN1907936A (en) * | 2004-12-19 | 2007-02-07 | 南京莱因医药科技有限公司 | Synthesis method of rhein and Diacerein |
Non-Patent Citations (2)
| Title |
|---|
| 张湛赋编著: "Diels-Alder反应", 《有机化学反应类型概论》 * |
| 郭书好主编: "氯乙烯", 《有机化学》 * |
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