CN102212101B - Method for preparing dihydrocholesterol and cholestanone - Google Patents
Method for preparing dihydrocholesterol and cholestanone Download PDFInfo
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- CN102212101B CN102212101B CN2011100974664A CN201110097466A CN102212101B CN 102212101 B CN102212101 B CN 102212101B CN 2011100974664 A CN2011100974664 A CN 2011100974664A CN 201110097466 A CN201110097466 A CN 201110097466A CN 102212101 B CN102212101 B CN 102212101B
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Abstract
The invention discloses a dihydrocholesterol preparation method. Cholesterin and hydrogen serve as the raw materials; the raw materials are subjected to a hydrogenation reaction in the presence of raney nickel or palladium charcoal or platinum carbon catalyst at the temperature of 30 to 85 DEG C in a low-carbon alcohol solvent with 1-4 carbon atoms; after the reaction, dihydrocholesterol is obtained through separation and drying; and the yield is more than or equal to 95 percent and the purity is more than or equal to 96 percent. During the dihydrocholesterol preparation, the dihydrocholesterol serves as the raw material; the raw material is subjected to oxidation reaction for at least 2 hours with oxidizers, such as potassium permanganate or potassium dichromate or a Jone reagent and the like, in a solvent, such as tert-butyl alcohol or water or acetone and the like, at the temperature of more than or equal to 25 DEG C until the boiling point of the solvent; after the reaction, the cholestanone is obtained through separation and drying; and the yield is more than or equal to 92 percent and the purity is more than or equal to 97 percent. The preparation method has mild hydrogenation and oxidation conditions, and simple process, is smooth in reaction, stable in quality, and convenient to operate, and is applicable to scale production. The preparation method also has the advantages of small catalyst amount, regeneration, solvent recovery and no three-waste discharge.
Description
The present invention is one and divides an application.The applying date 2009.03.13 of original application, application number 200910116337.8, invention and created name: the preparation method of a kind of beta-cholestanol and choleste alkyl ketone.
One, technical field
The present invention relates to the preparation method of steroid, specifically the preparation method of 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 the physiologically active substances such as synthetic bile acid, steroid hormone, adrenocortical hormone, oestrogenic hormon, male sex hormone, in human body, be combined salify with lipid acid or bile acide, but grease in the emulsification enteric cavity, increase the lipase action site, be convenient to oil and fat assimilation and absorb.
Find according to the study that in addition beta-cholestanol and choleste alkyl ketone can be used as the raw material of dehydroepiandros-sterone (DHEA), DHEA causes the extensive concern of the state medicine sectors such as U.S., method, day already because of its anti-aging effects.Studies show that in a large number DHEA is not only anti-ageing, also prevention and the treatment of diabetes, heart trouble, mammary cancer, uterus carcinoma are had 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 cholesterol, 60-75 ℃ of synthesizing dihydro cholesterol, the purified rear yield of crude product reaches 80%, the 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 only is 75%.The method exists certain drawback to produce the chromium ion contaminate environment such as: used oxygenant PDC (pyridinium dichromate); Reaction needs nitrogen protection; Solvent needs new processing etc.
Three, summary of the invention
The present invention is directed to the existing weak point of above-mentioned prior art, 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 take cholesterol as raw material, and hydrogenation obtains beta-cholestanol, and the beta-cholestanol oxidation obtains choleste alkyl ketone, and reaction formula is as follows:
The preparation method of this beta-cholestanol is the liquid phase catalytic hydrogenation method take cholesterol and hydrogen as raw material, comprise hydrogenation, separation and drying, difference with the prior art be described hydrogenation be cholesterol under low-carbon alcohol solvent catalyst neutralisation existence condition, stir pass into hydrogen when being warming up to 30～65 ℃, in 40～85 ℃ of lower reactions at least 3 hours, reaction finishes after heat filter, washing leaching cake, concentrated filtrate, recovery solvent, cooling, the beta-cholestanol crystallization, separation, drying obtain beta-cholestanol again.
Described solvent low-carbon alcohol is selected from the alcohol of 1-4 carbon atom, such as one or more alcohol mixtures in methyl alcohol, ethanol, ethylene glycol, 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 cholesterol.
The preparation method of this choleste alkyl ketone is as raw material take beta-cholestanol, comprise oxidation, separation and drying, difference with the prior art be described oxidation be beta-cholestanol in solvent by oxygenant in temperature 〉=25 ℃ until oxidizing reaction at least 2 hours under solvent boiling point (the being reflux state this moment) condition, reaction finishes the after heat filter, washing leaching cake, concentrated filtrate, recovery solvent, cooling, the choleste alkyl ketone crystallization, separation, drying obtain choleste alkyl ketone again.
The actual temp of oxidizing reaction is determined by the catalysts and solvents test of selecting.
Described solvent is selected from the trimethyl carbinol or water or acetone or acetic acid etc.
Described oxygenant is selected from potassium permanganate or potassium bichromate 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 technique, makes the cost decrease.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 cholesterol 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, as seen: 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 cholesterol 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 the 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 in three mouthfuls of glass flask of reflux condensing tube and cholesterol 3.2g is warming up to 65 ℃, pass into hydrogen under stirring, be warming up to 82 ℃, reaction 5h, filtered while hot, washing, concentrated, the rear suction filtration of cooling of filtrate namely get beta-cholestanol 2.95g, purity 97%.
2, get cholesterol 3.2g, Virahol 180mL, Pt/C 20mg, operation obtains beta-cholestanol 3.0g, purity 96% with example 1.
3, get cholesterol 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, then will be heated in advance 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 filtrate 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 potassium bichromate 4.41g (0.015mol), be heated to 30-35 ℃, keep thermotonus 2h, after reacting completely while hot suction filtration, wash, get the filtrate distillating recovering solvent, the cooling after suction filtration, be drying to obtain choleste alkyl ketone 3.6g, purity 96%.
6,3.9g (0.01mol) beta-cholestanol is added to the water, is heated to 50-60 ℃, then will be heated in advance 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 filtrate 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 choleste alkyl ketone take beta-cholestanol as raw material, comprises oxidation, separation and drying, it is characterized in that: the 3.9g beta-cholestanol is dissolved in the 40mL trimethyl carbinol, is heated to backflow, then will be heated in advance closely boil, contain 2.37g KMnO
4The 20mL aqueous solution adds wherein; Keep temperature, reflux two hours; After reacting completely while hot suction filtration, wash, get the filtrate distillating recovering solvent, cooling, suction filtration, be drying to obtain the choleste alkyl ketone 3.3g of purity 97%.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011100974664A CN102212101B (en) | 2009-03-13 | 2009-03-13 | Method for preparing dihydrocholesterol and cholestanone |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011100974664A CN102212101B (en) | 2009-03-13 | 2009-03-13 | Method for preparing dihydrocholesterol and cholestanone |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2009101163378A Division CN101492488B (en) | 2009-03-13 | 2009-03-13 | Method of preparing dihydrogen cholesterol and choleste alkyl ketone |
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| CN102212101A CN102212101A (en) | 2011-10-12 |
| CN102212101B true CN102212101B (en) | 2013-01-16 |
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| JP2017533176A (en) * | 2014-09-02 | 2017-11-09 | ネステク ソシエテ アノニム | Use of dihydrocholesterol |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1795201A (en) * | 2003-04-24 | 2006-06-28 | 姜宪中 | Process for preparing guggulsterones and guggulsterol |
| CN101012264A (en) * | 2007-02-09 | 2007-08-08 | 中国科学院上海有机化学研究所 | Method of synthesizing pig ectohormone |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1795201A (en) * | 2003-04-24 | 2006-06-28 | 姜宪中 | Process for preparing guggulsterones and guggulsterol |
| CN101012264A (en) * | 2007-02-09 | 2007-08-08 | 中国科学院上海有机化学研究所 | Method of synthesizing pig ectohormone |
Non-Patent Citations (1)
| Title |
|---|
| Naoshi Mori et al..Facile oxidative conversion of alcohols to esters using molecular iodine.《Tetrahedron》.2005,第61卷5915-5925. * |
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