CN101492488B - Method of preparing dihydrogen cholesterol and choleste alkyl ketone - Google Patents
Method of preparing dihydrogen cholesterol and choleste alkyl ketone Download PDFInfo
- Publication number
- CN101492488B CN101492488B CN2009101163378A CN200910116337A CN101492488B CN 101492488 B CN101492488 B CN 101492488B CN 2009101163378 A CN2009101163378 A CN 2009101163378A CN 200910116337 A CN200910116337 A CN 200910116337A CN 101492488 B CN101492488 B CN 101492488B
- Authority
- CN
- China
- Prior art keywords
- reaction
- solvent
- equal
- cholestanol
- beta
- 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
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a dihydrocholesterol preparation method, which takes cholesterin and hydrogen as the raw materials. The raw materials undergo hydrogenation reaction with the presence of raney nickel or palladium charcoal or platinum carbon catalyst under 30 to 85 DEG C in low-carbon alcohol solvent with 1-4 carbon atoms; after the reaction, dihydrocholesterol is acquired through separation and drying; the yield is equal to or more than 95 percent and the purity is equal to or more than 96 percent. The dihydrocholesterol preparation takes dihydrocholesterol as the raw material; the raw material undergoes oxidation reaction for at least 2 hours with potassium permanganate or potassium dichromate or Jone oxidizer in tert-butyl alcohol or water or acetone solvent at the temperature equal to or more than 25 DEG C until the boiling point of the solvent; after the reaction, cholestanone is acquired through separation and drying; the yield is equal to or more than 92 percent and the purity is equal to or more than 97 percent. The invention with mild hydrogenation and oxidation conditions, smooth reaction, stable quality, simple process and convenient operation is applicable to scale production. The invention also has the advantages of less catalyst amount, regeneration, solvent recovery and no three-waste discharge.
Description
One, technical field
The present invention relates to the preparation method of steroid, the preparation method of specifically a kind of beta-cholestanol and choleste alkyl ketone.
Two, background technology
Beta-cholestanol and choleste alkyl ketone (having another name called cholestanone) are the precursors of physiologically active substances such as synthetic bile acid, steroid hormone, adrenocortical hormone, oestrogenic hormon, male sex hormone; In human body, combine salify with lipid acid or bile acide; But grease in the emulsification enteric cavity; Increase the lypase action site, be convenient to oil and fat assimilation and absorb.
According to discovering that beta-cholestanol and choleste alkyl ketone can be used as the raw material of dehydroepiandros-sterone (DHEA), DHEA causes the extensive concern of state's medicine and pharmacology circle such as U.S.A, method, day already because of its anti-aging effects in addition.Big quantity research shows that DHEA is not only anti-ageing, and also prevention and the treatment to mellitus, heart trouble, mammary cancer, uterus carcinoma has obvious effect.
Beta-cholestanol can also add in the daily necessities such as toothpaste and can be used as anti-inflammatory agent in addition.
China reports early the preparation method of beta-cholestanol and choleste alkyl ketone; The Zhang Gongcheng of Lanzhou University etc. have just reported as far back as 1989 and have utilized glacial acetic acid as solvent; Platinum oxide is as the catalyst SUV, and at 60-75 ℃ of synthesizing dihydro SUV, the purified back of crude product yield reaches 80%; This method yield is lower, and thick product needs recrystallization; The synthetic of choleste alkyl ketone is in the new DMF of steaming, utilizes PDC oxidation beta-cholestanol under the nitrogen protection, and thick product yield behind extraction, column chromatography, recrystallization is merely 75%.This method exists certain drawback to produce the chromium ion contaminate environment like: used oxygenant PDC (pyridinium dichromate); The reaction needs nitrogen protection; Solvent needs new processing etc.
Three, summary of the invention
The present invention is directed to above-mentioned existing in prior technology weak point, aim to provide the preparation method of a kind of beta-cholestanol and choleste alkyl ketone, technical problem to be solved is the processing condition of selecting environment amenable hydrogenation and oxidation.
Technical solution problem of the present invention adopts following technical scheme.
The preparation of beta-cholestanol of the present invention and choleste alkyl ketone is a raw material with the SUV, and hydrogenation obtains beta-cholestanol, and the beta-cholestanol oxidation obtains choleste alkyl ketone, and reaction formula is following:
The preparation method of this beta-cholestanol is to be the liquid phase catalytic hydrogenation method of raw material with SUV and hydrogen; Comprise hydrogenation, separation and drying; Difference with the prior art is that described hydrogenation is that SUV stirs feeding hydrogen when being warming up to 30～65 ℃, reacted at least 3 hours down in 40～85 ℃ under low-carbon alcohol solvent catalyst neutralisation existence condition; Reaction finishes after heat filter, washing leaching cake, concentrated filtrate, recovery solvent, cooling; The beta-cholestanol crystallization is separated out, and separation, drying obtain beta-cholestanol again.
Described solvent low-carbon alcohol is selected from the alcohol of 1-4 carbon atom, like one or more alcohol mixtures in methyl alcohol, ethanol, terepthaloyl moietie, propyl alcohol, Virahol, butanols, the isopropylcarbinol.Particular methanol or/and ethanol or/and propyl alcohol or/and Virahol.
Described catalyzer is selected from Raney's nickel (Raney-Ni) or palladium carbon (Pd/C) or platinum carbon (Pt/C), and its consumption is the 0.05-0.25% (mass percent) of SUV.
The preparation method of this choleste alkyl ketone is to be raw material with the beta-cholestanol, comprises oxidation, separation and drying, difference with the prior art be described oxidation be beta-cholestanol in solvent by oxygenant in temperature >=25 ℃ under solvent boiling point (being reflux state this moment) condition oxidizing reaction at least 2 hours; Reaction finishes the after heat filter; Washing leaching cake, concentrated filtrate, recovery solvent, cooling; The choleste alkyl ketone crystallization is separated out, and separation, drying obtain choleste alkyl ketone again.
The actual temp of oxidizing reaction is confirmed by catalyzer of selecting and solvent test.
Described solvent is selected from the trimethyl carbinol or water or acetone or acetate etc.
Described oxygenant is selected from potassium permanganate or SRM 935a or Jone reagent or perchlorate or Manganse Dioxide etc.The consumption of oxygenant is 1.5～3: 1 for the mol ratio of itself and raw material beta-cholestanol.
This hydrogenation and method for oxidation mild condition, not only reacting balance is easy to control, and the separation after the reaction end is easier, has particularly omitted being further purified of product, has simplified technology, and cost is reduced significantly.Catalyst levels is few and renewable, and solvent also reclaims, and three-waste free discharge is environmentally friendly.Resulting product purity is high, and yield is high.The yield of beta-cholestanol >=95%, purity >=96%, the yield of choleste alkyl ketone >=92%, purity >=97%.
Four, description of drawings
Fig. 1 is the nuclear magnetic resonance spectroscopy spectrogram of SUV raw material.
Fig. 2 is the nuclear magnetic resonance spectroscopy spectrogram of product beta-cholestanol.
Fig. 3 is the nuclear magnetic resonance spectroscopy spectrogram of product choleste alkyl ketone.
Comparison diagram 1, Fig. 2 and Fig. 3; It is thus clear that: it is the chemical shift of hydrogen on the alcoholic extract hydroxyl group for chemical shift 3.65 places of hydrogen on two keys that 5.45 places are very clearly arranged in the SUV raw material; And just do not have to occur the chemical shift of hydrogen on two keys on the corresponding beta-cholestanol spectrogram, keep the chemical shift of hydrogen on the alcoholic extract hydroxyl group; Corresponding choleste alkyl ketone had not both had to occur the chemical shift of hydrogen on two keys, the chemical shift of hydrogen on the alcoholic extract hydroxyl group do not occur yet.By forming of provable beta-cholestanol of above analysis and choleste alkyl ketone.
Five, embodiment
(1) preparation of beta-cholestanol
1, is equipped with and adds reaction solvent ethanol 150mL, Pd/C catalyzer 32mg and SUV 3.2g in three mouthfuls of glass flask of reflux condensing tube and be warming up to 65 ℃; Stir and feed hydrogen down; Be warming up to 82 ℃; Reaction 5h, filtered while hot, washing, filtrating concentrate, cooling back suction filtration, promptly get beta-cholestanol 2.95g, purity 97%.
2, get SUV 3.2g, Virahol 180mL, Pt/C 20mg, operation obtains beta-cholestanol 3.0g, purity 96% with example 1.
3, get SUV 3.2g, methyl alcohol 100mL, propyl alcohol 100mL, Raney-Ni 50mg, operation is with example 1.Obtain beta-cholestanol 2.8g, purity 96%.
(2) preparation of choleste alkyl ketone
4,3.9g (0.01mol) beta-cholestanol is dissolved in the 40mL trimethyl carbinol, is heated to backflow, will be heated in advance then and closely boil, contain 2.37g (0.015mol) KMnO
4The 20mL aqueous solution adds wherein; Keep temperature, reflux two hours; After reacting completely while hot suction filtration, wash, get the filtrating distillating recovering solvent, cooling, suction filtration, be drying to obtain choleste alkyl ketone 3.3g, purity 97%.
5,3.9g (0.01mol) beta-cholestanol is dissolved in the 20mL acetone; Directly add SRM 935a 4.41g (0.015mol); Be heated to 30-35 ℃; Keep thermotonus 2h, after reacting completely while hot suction filtration, wash, get the filtrating distillating recovering solvent, cooling back suction filtration, be drying to obtain choleste alkyl ketone 3.6g, purity 96%.
6,3.9g (0.01mol) beta-cholestanol is added in the entry, be heated to 50-60 ℃, will be heated in advance then and closely boil, contain 3.95g (0.025mol) KMnO
4The 20mL aqueous solution adds wherein; Keep thermotonus 4h; After reacting completely while hot suction filtration, washing, ethyl alcohol recrystallization, be drying to obtain choleste alkyl ketone 2.8g, purity 98%.
7,3.9g (0.01mol) beta-cholestanol is dissolved in the 20mL acetone, is heated to 25 ℃, then the Jone reagent 10mL for preparing is added wherein; Heat tracing three hours; After reacting completely while hot suction filtration, wash, get the filtrating distillating recovering solvent, thick product dissolve with ethanol, suction filtration, distillating recovering solvent are drying to obtain choleste alkyl ketone 3.5g, purity 97%.
Claims (1)
1. the preparation method of a beta-cholestanol is to be the liquid phase catalytic hydrogenation method of raw material with SUV and hydrogen, comprises hydrogenation, separation and drying; It is characterized in that: in three mouthfuls of glass flask of reflux condensing tube are housed, add reaction solvent ethanol 150mL, Pd/C catalyzer 32mg and SUV 3.2g, be warming up to 65 ℃, stir and feed hydrogen down; Be warming up to 82 ℃, reaction 5h, filtered while hot, washing, filtrating concentrate, cooling back suction filtration; Promptly get beta-cholestanol 2.95g, purity 97%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101163378A CN101492488B (en) | 2009-03-13 | 2009-03-13 | Method of preparing dihydrogen cholesterol and choleste alkyl ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101163378A CN101492488B (en) | 2009-03-13 | 2009-03-13 | Method of preparing dihydrogen cholesterol and choleste alkyl ketone |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100974664A Division CN102212101B (en) | 2009-03-13 | 2009-03-13 | Method for preparing dihydrocholesterol and cholestanone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101492488A CN101492488A (en) | 2009-07-29 |
| CN101492488B true CN101492488B (en) | 2012-01-11 |
Family
ID=40923294
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101163378A Expired - Fee Related CN101492488B (en) | 2009-03-13 | 2009-03-13 | Method of preparing dihydrogen cholesterol and choleste alkyl ketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101492488B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017533176A (en) * | 2014-09-02 | 2017-11-09 | ネステク ソシエテ アノニム | Use of dihydrocholesterol |
| CN115724897A (en) * | 2021-08-31 | 2023-03-03 | 四川澄华生物科技有限公司 | Oxidation impurity removal method for cholestanic acid and derivatives thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0685488A1 (en) * | 1993-12-16 | 1995-12-06 | Nippon Fine Chemical Co., Ltd. | Process for producing high-purity cholesterol |
| US20070209924A1 (en) * | 2006-03-07 | 2007-09-13 | Vanier Grace S | Method and apparatus for conducting microwave assisted organic reactions with gas-phase reactants |
-
2009
- 2009-03-13 CN CN2009101163378A patent/CN101492488B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0685488A1 (en) * | 1993-12-16 | 1995-12-06 | Nippon Fine Chemical Co., Ltd. | Process for producing high-purity cholesterol |
| US20070209924A1 (en) * | 2006-03-07 | 2007-09-13 | Vanier Grace S | Method and apparatus for conducting microwave assisted organic reactions with gas-phase reactants |
Non-Patent Citations (5)
| Title |
|---|
| Kuniaki Okamoto,et al..Recoverable, Reusable, Highly Active, and Sulfur-Tolerant Polymer Incarcerated Palladium for Hydrogenation.《J.Org.Chem.》.2004,第69卷2871-2873. * |
| KuniakiOkamoto et al..Recoverable |
| Min Serk Kwon,et al..Palladium Nanoparticles Entrapped in Aluminum Hydroxide:Dual Catalyst for Alkene Hydrogenation and Aerobic Alcohol Oxidation.《ORGANIC LETTERS》.2005,第7卷(第6期),1077-1079. * |
| Nicoletta Ravasio,et al..Selective Hydrogenations Promoted by Copper Catalysts. 2. Hydrogen-Transfer Reactions Leading to Stereoselective Hydrogenation of Δ5-3β-Sterols to 5β-Derivatives.《J. Org. Chem. 》.1993,第58卷1259-1261. * |
| 张攻成等.生物标志化合物的合成研究III.5α-胆甾烷和5β-胆甾烷的合成.《应用化学》.1989,第6卷(第4期),50-53. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101492488A (en) | 2009-07-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108676049A (en) | A kind of preparation method of Austria's shellfish cholic acid, ursodesoxycholic acid and 7- Ketocholic acid | |
| CN106749466B (en) | A kind of preparation method of high-purity Austria shellfish cholic acid | |
| CN105399791B (en) | A kind of preparation method of betamethasone intermediate | |
| CN109912676B (en) | Preparation method of 3 beta-ursodesoxycholic acid | |
| CN110003298B (en) | Synthetic method of promestrene | |
| CN105153258B (en) | The preparation method of 3-beta-hydroxy-androstane-17-ketone | |
| CN104530166A (en) | Method for selective reduction of 4, 6-conjugated diene-3-one steroid | |
| CN101863948B (en) | High-purity (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17-diol or composition thereof and preparation method thereof | |
| CN106046095A (en) | Synthetic method of 6-ethylchenodeoxycholic acid | |
| CN101492488B (en) | Method of preparing dihydrogen cholesterol and choleste alkyl ketone | |
| CN102351778A (en) | Preparation method of arbidol hydrochloride | |
| CN102212101B (en) | Method for preparing dihydrocholesterol and cholestanone | |
| CA2480151A1 (en) | C-17 spirolactonization and 6,7 oxidation of steroids | |
| CN105669815A (en) | Preparation method of 3Alpha-hydrol-7-oxo-5Beta-cholanic acid | |
| CN108752415A (en) | A kind of Finasteride chiral impurity（5 β-Finasterides）Synthesis and purification process | |
| CN102134266A (en) | Preparation method of melengestrol acetate | |
| CN111116692A (en) | Synthesis method of high-purity selamectin | |
| CN113999167B (en) | Preparation method of 4-chloro-2,6-dimethyl-3-nitropyridine | |
| EP3744711A1 (en) | Method for preparing mesaconine and related intermediaries | |
| WO2023000636A1 (en) | Method for synthesis of (3-fluorooxetan-3-yl)methyl 4-methylbenzenesulfonate | |
| CN101555223B (en) | Pirlimycin intermediate and preparation method thereof | |
| CN107663221A (en) | A kind of preparation method of shellfish cholic acid difficult to understand | |
| CN101974058B (en) | Purification technology of pregnenolone acetate | |
| CN103864747B (en) | The total synthesis method of mangostin | |
| CN114685410B (en) | Preparation method of butylphthalide |
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: 20120111 Termination date: 20130313 |