CN1800134A - Diacetyl rhein preparation method - Google Patents
Diacetyl rhein preparation method Download PDFInfo
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- CN1800134A CN1800134A CN 200610049171 CN200610049171A CN1800134A CN 1800134 A CN1800134 A CN 1800134A CN 200610049171 CN200610049171 CN 200610049171 CN 200610049171 A CN200610049171 A CN 200610049171A CN 1800134 A CN1800134 A CN 1800134A
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Abstract
The invention provides a method for preparing diacetyl rheinic acid. It uses residues after extracting aloinose as starting matter and is obtained by hydrolyzing, acetylating and oxidant. The residues comprises: aloe glycosides, sennoside, aloe-emodin, chrysophanol, aloenin and aloin and corbit substance which is 10%-20% of the residues' weight.
Description
Technical field
The present invention relates to a kind of method for preparing diacetyl rhein.
Background technology
Diacetyl rhein is a kind of new interleukin/β/(inhibitor of L-/β), treatment osteoarthritis, and the slow arthritic medicine of drawing property. The structural formula of diacetyl rhein
Diacetyl rhein is because the resource of various countries is different, and its synthetic initiation material is not quite similar, but the preparation feedback after mostly needing after purifying, just can carry out. Such as, this product of internationalized production rushes down leaf as initiation material take Pan at first, after extraction Pan is rushed down the leaf glucoside, gets through the hydrolysis oxidation acetylation again. Also having more American-European countries to use aloe ferox Miller instead is that initiation material is produced this product, and they extract barbaloin in aloe after, obtain diacetyl rhein with oxydrolysis, this process route subject matter is, necessary purification aloin, or aloe-emodin, production cost is higher.
Summary of the invention
Technical problem to be solved by this invention provides the method for preparing diacetyl rhein that a kind of preparation method is simple, production cost is low. The present invention by the following technical solutions for this reason: the residue that it is extracted behind the aloe polysaccharide by aloe is starting material, and makes through hydrolysis, acetylation, oxidation successively.
Extracting aloe polysaccharide in aloe, is more widely aloe processing and utilization method of the world and domestic application. Its residue includes barbaloin, Pan is rushed down the anthraquinones such as glycosides, aloe-emodin, Chrysophanol, aloearbonaside, aloe rheum officinale glucoside, and these materials generally account for residue weight 10%～20%, in the past generally as offal treatment.
Adopt method of the present invention to prepare diacetyl rhein, initiation material adopts the residue after aloe is extracted aloe polysaccharide, wide material sources, price are low, save in process of production the complicated processes of monomer separation, and in process of production, each step reaction had both reduced production cost and had also improved product yield all at the purification target product.
The present invention also can adopt following further technical scheme simultaneously:
The said hydrolyzed process uses ferric trichloride and/or ferric sulfate to be oxidant, make solvent with 0.5-5N hydrochloric acid, the weight ratio of raw material and hydrochloric acid is 1: 5～50, hydrolysis temperature: 90～110 ℃, time is 3～10 hours, and the mol ratio of barbaloin is 1: 5～30 in oxidant consumption and the raw material. Ferric trichloride can be anhydrous or with water, ferric sulfate can be the band crystallization water or not be with the crystallization water.
Acetylation uses acid anhydrides as acetylizing agent; anhydrous sodium acetate, acetic anhydride potassium, pyridine or picoline are as catalyst; the weight ratio of raw material hydrolysate and aceticanhydride is 1: 8～20 times; 100～105 ℃ of acetylation temperature; time is 4～5 hours, and catalyst amount is 0.3-1.0 times of raw material hydrolysate weight.
The water of oxidizing process use chromium trioxide or acetum are as oxidant, and the weight ratio of chromium trioxide and acetylation afterproduct is 1: 1.2～1.5, and oxidizing reaction temperature is 28～45 ℃, 4～6 hours time.
In order further to improve stability and the purity of product, the present invention after oxidation, also can comprise successively to products therefrom purify, conversion, dechromisation, acidification step.
Purification process adopts mixture with aceticanhydride and glacial acetic acid or N.N-dimethylacetylamide (being DMFA) as solvent.
Be solvent with ethanol or acetone in the conversion process, use the potassium acetate aqueous solution as the salify transforming agent.
Be that EDTA or disodium EDTA are made chromium remover with ethylenediamine tetra-acetic acid in the dechromisation process.
In the acidization, with 40%-60% ethanol as dechromisation after the solvent of material, with dilute sulfuric acid, watery hydrochloric acid, phosphoric acid,diluted regulator solution to PH3～5.
Also products therefrom is carried out drying after acidifying, dry run was under vacuum condition, in 50～70 ℃ of dryings 12～20 hours.
Specific implementation process
The residue that the present invention is extracted behind the aloe polysaccharide by aloe is starting material, and makes diacetyl rhein through hydrolysis, acetylation, oxidation successively.
The said hydrolyzed process uses ferric trichloride and/or ferric sulfate to be oxidant, make solvent with 0.5-5N hydrochloric acid, the weight ratio of raw material and hydrochloric acid is 1: 5～50, hydrolysis temperature: 90～110 ℃, time is 3～10 hours, and the mol ratio of barbaloin is 1: 5～30 in oxidant consumption and the raw material. Ferric trichloride can be anhydrous or with water, ferric sulfate can be the band crystallization water or not be with the crystallization water.
Acetylation uses acid anhydrides as acetylizing agent; anhydrous sodium acetate, acetic anhydride potassium, pyridine or picoline are as catalyst; the weight ratio of raw material hydrolysate and aceticanhydride is 1: 8～20 times; 100～105 ℃ of acetylation temperature; time is 4～5 hours, and catalyst amount is 0.3-1.0 times of raw material hydrolysate weight.
The water of oxidizing process use chromium trioxide or acetum are as oxidant, and the weight ratio of chromium trioxide and acetylation afterproduct is 1: 1.2～1.5, and oxidizing reaction temperature is 28～45 ℃, 4～6 hours time.
In order further to improve stability and the purity of product, the present invention after oxidation, also can comprise successively to products therefrom purify, conversion, dechromisation, acidification step.
Purification process adopts the mixture of aceticanhydride and glacial acetic acid or N.N-dimethylacetylamide (being DMFA) as solvent.
Be solvent with ethanol or acetone in the conversion process, use the potassium acetate aqueous solution as the salify transforming agent, the product after the purification and the weight ratio of potassium acetate are 1: 0.8～1.0.
Be that EDTA or disodium EDTA are made chromium remover with ethylenediamine tetra-acetic acid in the dechromisation process.
In the acidization, with 40%-60% ethanol as dechromisation after the solvent of material, with dilute sulfuric acid, watery hydrochloric acid, phosphoric acid,diluted regulator solution to PH3～5.
Also products therefrom is carried out drying after acidifying, dry run was under vacuum condition, in 50～70 ℃ of dryings 12～20 hours.
Embodiment 1
The preparation of hydrolysate:
In the flask of 2000ml, drop into residue 100g, ferric chloride (FeCl36H2O) 100g after aloe is extracted aloe polysaccharide, the mol ratio of barbaloin is approximately 1: 20 in ferric trichloride and the residue, water 800ml, 2-5N hydrochloric acid 800ml added the thermal agitation temperature rising reflux 8 hours, react complete, cold filtration, filter cake washes with water, the dry total HPLC of solid matter 28.0g (total anthraquinones) 56.5%, the molar yield 88% of getting. In this process, after the partial impurities in the residue is hydrolyzed, be removed with filtrate.
Concrete reaction equation:
R wherein1The grape base, hydroxyl, R2Be methylol, methyl, carboxylic acid group, R3Be the grape base.
Acetylation:
Add the 28.0g hydrolysate in the dry flask of 500ml, total HPLC56.5% contains anthraquinones 15.82g, 14g anhydrous sodium acetate and aceticanhydride 280g, be warmed up to 100 ℃, be incubated 4-5.0 hour, cool off 60 ℃, the recovered under reduced pressure aceticanhydride gets semi-solid material, adds toluene 100ml, and recovered under reduced pressure is to doing again, add again toluene 400ml, temperature rising reflux 1.0 hours cools off 40 ℃, suction filtration, filter cake 60ml hot toluene is washed, recovered under reduced pressure toluene, 300ml toluene, 3-5 ℃ of raffinate cooling, crystallization 1.0 hours, suction filtration with the toluene recrystallization once, can be expected 20.7g again, and crystalline mother solution contains material 2.9g and can expect altogether: 23.6, total HPLC 〉=95%, molar yield is 89%. In this process, after the partial impurities in the residue is reacted, be removed with filter cake.
R
2'-be CH2OAC，CH
3, the carboxylic acid group
Oxidizing process
Add the 20.0g acetylate in the 1000ml flask, total HPLC 〉=95% adds 200ml aceticanhydride and 400ml glacial acetic acid; intensification 50-55 ℃; become a solution, again be cooled to 35 ℃, in another 500ml flask, add 14g chromium trioxide and 220ml glacial acetic acid; water 222ml; wiring solution-forming at room temperature, then last wiring solution-forming is added drop-wise in the above-mentioned reactant liquor about 2.0 hours; 40-45 ℃ of control temperature; drip and finish, be incubated 4-6 hour, again oxidation solution is poured in the frozen water; faint yellow Precipitation; filter washing, drying; obtaining diacetyl rhein crude product 17.4gHPLC is 95%, and molar yield is 90%. In this process, after the partial impurities in the residue is reacted, be removed with filtrate.
ACO represents acetyl group
Making with extra care of diacerein:
With diacetyl rhein crude product 15.0g, 60mlDMFA and aceticanhydride 0.6ml are warmed up to 100-105 ℃, are incubated 1.0 hours, directly only become solution, cool off about 0 ℃ again, filter and wash to get wet feed 23.0g with acetone.
Wet feed 23.0g is put in the 225ml acetone, add entry 7.5ml and slowly add potassium acetate 13.0g, wiring solution-forming, and with in this solution adding reactant liquor, then temperature rising reflux is 1.5 hours, remove by filter while hot insoluble matter, filtrate is cooled off 5-10 ℃ again, crystallization 1.5 hours leaches diacerein sylvite, filter, wash with acetone.
Dechromisation and acidifying
Sylvite is dissolved in 50% ethanol, among the 300ml, keeps 20-30 ℃ of temperature, add EDTA, stirring and dissolving also adds the 1.2g active carbon, stirs 1.0 little filtrations, transfers PH=4.0 with 6N phosphoric acid, filter washing, drain, dryly in 50-70 ℃ of vacuum must expect 12.5g, HPLC is 98.6%, molar yield 83.3%.
In above subtractive process, also can further remove the impurity in the residue.
Below be the parameter summary sheet of embodiment 2～5:
| Step | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| Hydrolysis | Anhydrous ferric trichloride is oxidant, and 5N hydrochloric acid is made solvent, and the weight ratio of raw material and hydrochloric acid is 1: 5, and hydrolysis temperature is controlled at 90～110 ℃, and the time is 3 hours, and the mol ratio of barbaloin is 1: 30 in oxidant consumption and the raw material. Total HPLC 54.6 % of dried solid matter, molar yield 0.86. | Ferric sulfate with the crystallization water is oxidant, makes solvent with 0.5N hydrochloric acid, and the weight ratio of raw material and hydrochloric acid is 1: 50, hydrolysis temperature: 90～110 ℃, the time is 10 hours, and the mol ratio of barbaloin is 1: 5 in oxidant consumption and the raw material. Total HPLC 57.6 % of dried solid matter, molar yield 0.91 | Anhydrous ironic sulfate is oxidant, makes solvent with 3.5N hydrochloric acid, and the weight ratio of raw material and hydrochloric acid is 1: 20, hydrolysis temperature: 90～110 ℃, the time is 7 hours, and the mol ratio of barbaloin is 1: 5～10 in oxidant consumption and the raw material. Total HPLC 56.2 % of dried solid matter, molar yield 0.88 | Ferric chloride (FeCl36H2O) is oxidant, makes solvent with 1.5N hydrochloric acid, and the weight ratio of raw material and hydrochloric acid is 1: 35, hydrolysis temperature: 90～110 ℃, the time is 5 hours, and the mol ratio of barbaloin is 1: 15 in oxidant consumption and the raw material. Total HPLC 56.5 % of dried solid matter, molar yield 0.89 |
| Acetylation | Use acid anhydrides as acetylizing agent; acetic anhydride potassium is as catalyst, and the weight ratio of raw material hydrolysate and aceticanhydride is 1: 8 times, and the acetylation temperature is controlled at 100～105 ℃; time is 4～5 hours, and catalyst amount is 0.3 times of raw material hydrolysate weight. The total HPLC 95.6% of crystalline material, molar yield 0.88. | Use acid anhydrides as acetylizing agent, pyridine is as catalyst, and the weight ratio of raw material hydrolysate and aceticanhydride is 1: 20 times, and the acetylation temperature is controlled at 100～105 ℃, and the time is 4～5 hours, and catalyst amount is 1.0 times of raw material hydrolysate weight. The total HPLC 96.2% of crystalline material, molar yield 0.91. | Use acid anhydrides as acetylizing agent; picoline is as catalyst, and the weight ratio of raw material hydrolysate and aceticanhydride is 1: 12 times, and the acetylation temperature is controlled at 100～105 ℃; time is 4～5 hours, and catalyst amount is 0.5 times of raw material hydrolysate weight. The total HPLC 95.2% of crystalline material, molar yield 0.89. | Use acid anhydrides as acetylizing agent; picoline is as catalyst, and the weight ratio of raw material hydrolysate and aceticanhydride is 1: 17 times, and the acetylation temperature is controlled at 100～105 ℃; time is 4～5 hours, and catalyst amount is 0.8 times of raw material hydrolysate weight. The total HPLC 96% of crystalline material, molar yield 0.90. |
| Oxidation | Use chromium trioxide water | Use chromium trioxide vinegar | Use chromium trioxide vinegar | Use chromium trioxide water |
| Solution is as oxidant, and the weight ratio of chromium trioxide and acetylation afterproduct is 1: 1.2, and oxidizing reaction temperature is 28～31 ℃, 6 hours time. Obtain the diacetyl rhein crude product, HPLC is 96%, and molar yield is 0.91. | Acid solution is as oxidant, and the weight ratio of chromium trioxide and acetylation afterproduct is 1: 1.5, and oxidizing reaction temperature is 42～45 ℃, 4 hours time. Obtain the diacetyl rhein crude product, HPLC is 97.2%, and molar yield is 0.89. | Acid solution is as oxidant, and the weight ratio of chromium trioxide and acetylation afterproduct is 1: 1.3, and oxidizing reaction temperature is 30～34 ℃, 5 hours time. Obtain the diacetyl rhein crude product, HPLC is 96.5%, and molar yield is 0.91. | Solution is as oxidant, and the weight ratio of chromium trioxide and acetylation afterproduct is 1: 1.4, and oxidizing reaction temperature is 36～40 ℃, 4.5 hours time. Obtain the diacetyl rhein crude product, HPLC is 97.5%, and molar yield is 0.92. | |
| Purify | Adopt the mixture of aceticanhydride and glacial acetic acid as solvent. Quantity of solvent be 30 times to the diacetyl rhein crude product, the ratio of aceticanhydride and glacial acetic acid is 20: 80. | Adopt the mixture of aceticanhydride and glacial acetic acid as solvent. Quantity of solvent be 100 times to the diacetyl rhein crude product, the ratio of aceticanhydride and glacial acetic acid is 15: 85. | Adopt the mixture of aceticanhydride and glacial acetic acid as solvent. Quantity of solvent be 60 times to the diacetyl rhein crude product, the ratio of aceticanhydride and glacial acetic acid is 35: 65. | Adopt the mixture of aceticanhydride and DMFA as solvent. Quantity of solvent be 5 times to the diacetyl rhein crude product, the ratio of aceticanhydride and DMFA is 1: 4. |
| Transform | Use acetone to be solvent, the potassium acetate aqueous solution is as the salify transforming agent, and the product after the purification and the weight ratio of potassium acetate are 1: 0.8. | Use ethanol to be solvent, the potassium acetate aqueous solution is as the salify transforming agent, and the product after the purification and the weight ratio of potassium acetate are 1: 1.0. | Use acetone to be solvent, the potassium acetate aqueous solution is as the salify transforming agent, and the product after the purification and the weight ratio of potassium acetate are 0.9. | Use ethanol to be solvent, the potassium acetate aqueous solution is as the salify transforming agent, and the product after the purification and the weight ratio of potassium acetate are 0.85. |
| Dechromisation | With embodiment 1 | Make chromium remover with disodium EDTA | With embodiment 1 | Disodium EDTA is made chromium remover |
| Acidifying | With 40% ethanol as dechromisation after the solvent of material, with the dilute sulfuric acid regulator solution to PH3～5. | With 60% ethanol as dechromisation after the solvent of material, with rare phosphorus regulator solution to PH3～5. | With 50% ethanol as dechromisation after the solvent of material, with the dilute sulfuric acid regulator solution to PH3～5. | With 40% ethanol as dechromisation after the solvent of material, with the phosphoric acid,diluted regulator solution to PH3～5. |
| Dry | The method of pressing embodiment 1 is dry. Product HPLC is 99.1%, yield % 82. | The method of pressing embodiment 1 is dry. Product HPLC is 99.3%, yield % 84. | The method of pressing embodiment 1 is dry. Product HPLC is 98.5%, yield % 83. | The method of pressing embodiment 1 is dry. Product HPLC is 98.9%, yield %82.3. |
Embodiment 2～5 other concrete steps identical with embodiment 1.
Claims (10)
1, a kind of method for preparing diacetyl rhein is characterized in that the residue after it is by aloe extraction aloe polysaccharide is starting material, and makes through hydrolysis, acetylation, oxidation successively.
2, a kind of method for preparing diacetyl rhein as claimed in claim 1, it is characterized in that hydrolytic process uses ferric trichloride and/or ferric sulfate to be oxidant, make solvent with 0.5-5N hydrochloric acid, the weight ratio of raw material and hydrochloric acid is 1: 5～50, hydrolysis temperature: 90～110 ℃, time is 3～10 hours, and the mol ratio of barbaloin is 1: 5～30 in oxidant consumption and the raw material.
3, a kind of method for preparing diacetyl rhein as claimed in claim 1; it is characterized in that acetylation uses acid anhydrides as acetylizing agent; anhydrous sodium acetate, acetic anhydride potassium, pyridine or picoline are as catalyst; the weight ratio of raw material hydrolysate and aceticanhydride is 1: 8～20 times; 100～105 ℃ of acetylation temperature; time is 4～5 hours, and catalyst amount is 0.3-1.0 times of raw material hydrolysate weight.
4, a kind of method for preparing diacetyl rhein as claimed in claim 1; it is characterized in that oxidizing process uses the water of chromium trioxide or acetum as oxidant; the weight ratio of chromium trioxide and acetylation afterproduct is 1: 1.2～1.5; oxidizing reaction temperature is 28～45 ℃, 4～6 hours time.
5, such as claim 1,2,3 or 4 described a kind of methods that prepare diacetyl rhein, it is characterized in that it after oxidation, also comprise successively to products therefrom purify, conversion, dechromisation, acidification step.
6, a kind of method for preparing diacetyl rhein as claimed in claim 5 is characterized in that purification process adopts the mixture of aceticanhydride and glacial acetic acid or N.N-dimethylacetylamide as solvent.
7, a kind of method for preparing diacetyl rhein as claimed in claim 5 is characterized in that in the conversion process with ethanol or acetone being solvent, uses the potassium acetate aqueous solution as the salify transforming agent.
8, a kind of method for preparing diacetyl rhein as claimed in claim 5 is characterized in that making chromium remover with ethylenediamine tetra-acetic acid or disodium EDTA in the dechromisation process.
9, a kind of method for preparing diacetyl rhein as claimed in claim 5 is characterized in that in the acidization, with 40%-60% ethanol as dechromisation after the solvent of material, with dilute sulfuric acid, watery hydrochloric acid, phosphoric acid,diluted regulator solution to PH3～5.
10, a kind of method for preparing diacetyl rhein as claimed in claim 5 is characterized in that also products therefrom being carried out drying after acidifying, and dry run is under vacuum condition, in 50～70 ℃ of dryings 12～20 hours.
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| CN 200610049171 CN1800134A (en) | 2006-01-19 | 2006-01-19 | Diacetyl rhein preparation method |
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| CN 200610049171 CN1800134A (en) | 2006-01-19 | 2006-01-19 | Diacetyl rhein preparation method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102711519A (en) * | 2010-02-03 | 2012-10-03 | 森永乳业株式会社 | Method for manufacturing aloe powder |
| CN112279767A (en) * | 2020-10-29 | 2021-01-29 | 陕西嘉禾生物科技股份有限公司 | Preparation method of diacerein |
-
2006
- 2006-01-19 CN CN 200610049171 patent/CN1800134A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102711519A (en) * | 2010-02-03 | 2012-10-03 | 森永乳业株式会社 | Method for manufacturing aloe powder |
| CN112279767A (en) * | 2020-10-29 | 2021-01-29 | 陕西嘉禾生物科技股份有限公司 | Preparation method of diacerein |
| CN112279767B (en) * | 2020-10-29 | 2023-02-03 | 陕西嘉禾生物科技股份有限公司 | Preparation method of diacerein |
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