CN102702295A - Preparation method of 7-dehydrocholesterol - Google Patents
Preparation method of 7-dehydrocholesterol Download PDFInfo
- Publication number
- CN102702295A CN102702295A CN2012101630409A CN201210163040A CN102702295A CN 102702295 A CN102702295 A CN 102702295A CN 2012101630409 A CN2012101630409 A CN 2012101630409A CN 201210163040 A CN201210163040 A CN 201210163040A CN 102702295 A CN102702295 A CN 102702295A
- Authority
- CN
- China
- Prior art keywords
- dehydrocholesterol
- reaction
- preparation
- benzoate
- bromination
- 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.)
- Pending
Links
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
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Abstract
The invention discloses a preparation method of 7-dehydrocholesterol. The preparation method comprises four steps of esterifying, brominating, de-brominating, saponifying and hydrolyzing. In the brominating reaction process, the brominating agent, namely N-brominated succimide (NBS) with advantages of high location, high active bromine content, good storage stability and economic usage is selected. Due to the brominating agent, the side reaction is less during the preparation; the by-product is few and a plurality of steps of removing brominating by-products are saved; due to the mol concentration proportion of the method, the yield of the target product is notably improved.
Description
Technical field
The invention belongs to the organic synthesis field, relate to a kind of 7-dehydrocholesterol preparation method.
Background technology
Vitamin D3 500,000 I.U/GM is people and domestic animal, the domestic animal requisite liposoluble vitamin of growing, breed, earn a bare living and keep fit, and its main effect is to regulate alcium and phosphor metabolization, promotes that calcium phosphorus absorbs and the sclerotin calcification in the intestines, keeps the balance of blood calcium and serium inorganic phosphorus.Vitamin D3 500,000 I.U/GM be mainly used in 3 aspects such as pharmaceutical prepn, foodstuff additive and fodder additives, as pharmaceutical prepn, be mainly used in illnesss such as treatment rickets, richets, osteoporosis, thyroprivia clinically; As food beverage additive, it can make an addition in milk, milk-product, biscuit, candy and the various beverage, is used to prevent vitamin D deficiency; Vitamin D3 500,000 I.U/GM can increase the output of meat, egg, milk as the fodder additives of livestock and poultry, and can improve its nutritive value.
At present, Vitamin D3 500,000 I.U/GM 6000-8000t is produced in the whole world per year, is mainly produced by minority developed country.Every year the rope D3 demand of supporting one's family is surpassed 10000t in the world, the annual Vitamin D3 500,000 I.U/GM consumption of China has survey data to show that China will surpass 5000t very soon to the demand of Vitamin D3 500,000 I.U/GM more than 4000t.The Vitamin D3 500,000 I.U/GM of China is maximum with the feed additive industry consumption at present.The production key of Vitamin D3 500,000 I.U/GM is the production of its precursor 7 one dehydrocholesterols, and the output of 7 one dehydrocholesterols and quality product largely can determine the situation of Vitamin D3 500,000 I.U/GM.
Existing compound method has following several kinds: (1) with the SUV be raw material through esterification, oxygenant oxidations such as zirconium white or cobaltous acetate, again through reduction, eliminate and to obtain title product.(2) be raw material with 6-alkene cholesterol, with 4-phenyl-1,2,4-triazoline-3,5-diketone are protected the two keys on 6, with NaHCO3 and Jone ' S reagent oxidation, use sodium borohydride reduction then again, obtain the 7-dehydrocholesterol after the hydrolysis.(3) biological synthesis process is synthetic, and as being the synthetic title product of raw material with the lathosterol, the aforesaid method productive rate is generally not high.
Summary of the invention
To the deficiency of prior art, the present invention provides a kind of preparation method of 7-dehydrocholesterol, can effectively reduce the sub product kind, improves product yield.
To achieve these goals, technical scheme of the present invention is: a kind of 7-dehydrocholesterol preparation method is characterized in that: comprise the steps:
1) SUV and Benzoyl chloride 99min. are carried out esterification, make cholesterol benzoate;
2) cholesterol benzoate and bromide are positioned bromination reaction, make 7-bromo cholesterol benzoate;
3) 7-bromo cholesterol benzoate and pyridine are removed bromination reaction, make 7-dehydrocholesterol benzoic ether;
4) with 7-dehydrocholesterol benzoic ether and the Pottasium Hydroxide saponification reaction that is hydrolyzed, make title product 7-dehydrocholesterol;
The bromide of participating in bromination reaction further, said step 2) is a N-bromination succimide, is called for short NBS;
Further, the molar ratio of material that carries out esterification in the said step 1) is: SUV: Acetyl Chloride 98Min. 1:0.9-1:1.9, and the reaction times is 6-12h, temperature is 90-110 ℃;
Further, said step 2) molar ratio of material that carries out bromination reaction in is: cholesterol benzoate: N-bromination succimide 1:0.9-1:1.6, and the reaction times is 2-6h, temperature is 75-90 ℃;
Further, go the material ratio of bromination reaction to be in the said step 3): 7-bromo cholesterol benzoate: pyridine 1:1.0-1:1.7, the reaction times is 2-4h, temperature is 65-85 ℃;
Further, the material ratio of the saponification reaction that is hydrolyzed in the said step 4) is: 7-dehydrocholesterol benzoic ether: Pottasium Hydroxide 1:1.0-1:1.9, and the reaction times is 2-4h, temperature is 60-80 ℃.
The invention has the beneficial effects as follows: the high location of this technology bromination reaction adopts bromizating agent N-bromination succimide (NBS) as bromizating agent, and this bromizating agent has high location, active bromine content height, excellent storage stability, use economic dispatch advantage.Use this bromizating agent and make in the preparation process that side reaction is few and by product is few, saved many steps of removing brominated by products; And the volumetric molar concentration proportioning of this technology significantly improves the target product yield of this technology.
Embodiment
Below in conjunction with specific embodiment the present invention is done further explanation.
Embodiment 1
1, a kind of 7-dehydrocholesterol preparation method comprises the steps:
1) esterification
SUV+Benzoyl chloride 99min. → cholesterol benzoate
Molar ratio of material: SUV: Benzoyl chloride 99min. 1:1.5
The synthetic of SUV benzene methyl carries out in two steps, and the one, Benzoyl chloride 99min. synthetic, the 2nd, be raw material synthetic cholesterol benzoic ether with Benzoyl chloride 99min. and SUV.Specific embodiments is following:
The sulfur oxychloride that newly steams is at room temperature reacted 1h (sulfur oxychloride and benzoic mol ratio are 1.05 ︰ 1) with phenylformic acid at 50 ± 5 ℃, be warmed up to 90 ℃ then, reaction 2h.Normal pressure steams excessive sulfur oxychloride, and decompression steams Benzoyl chloride 99min. again, as the raw material of next step reaction.
SUV is dissolved in the exsiccant benzene, adds pyridine ［ W
SUV() ︰ V g
Benzene() ︰ V ml
Pyridine(ml)=1 ︰ 4 ︰ 1 ］, add Benzoyl chloride 99min. again, at room temperature reacted 15 minutes, slowly heating is warming up to 95 ℃, esterification 8h under this temperature then; The cooling back adds and benzene equal-volume 1NHCl solution, tells organic layer, and water layer is with anhydrous diethyl ether extraction three times.Merge organic layer and ether extraction liquid, behind anhydrous magnesium sulfate drying, boil off organic solvents such as ether, benzene, separate out thick product after the cooling.With absolute ethyl alcohol recrystallization 2-3 time, obtain white crystal, i.e. cholesterol benzoate.
2) bromination reaction: cholesterol benzoate+NBS → 7-bromo cholesterol benzoate molar ratio of material: cholesterol benzoate: NBS 1:1.5
Logical nitrogen protection in the reaction kettle, tetracol phenixin is made solvent, adds cholesterol benzoate, is heated to 84
℃, gradation adds NBS, adds a little Diisopropyl azodicarboxylate and makees initiator, and reaction 4h filters, and washes with ethanol, promptly gets 7-bromo cholesterol benzoate.
3) remove bromination reaction
7-bromo cholesterol benzoate+pyridine → 7-dehydrocholesterol benzoate
Molar ratio of material: 7-bromo cholesterol benzoate: pyridine 1:1.5
7-bromo cholesterol benzoate and pyridine react in ethanol and generate 7-dehydrocholesterol benzoate, and after the optimization, the reaction times is 3h, and temperature is 78 ℃, gets 7-dehydrocholesterol benzoate.
4) hydrolysis saponification reaction
7-dehydrocholesterol benzoate+Pottasium Hydroxide → 7-dehydrocholesterol
Molar ratio of material: 7-dehydrocholesterol benzoic ether: Pottasium Hydroxide 1:1.5
7-dehydrocholesterol benzoate and Pottasium Hydroxide react in ethanol and generate the 7-dehydrocholesterol, and the reaction times is 3h, and temperature is 78 ℃, get the 7-dehydrocholesterol.
Embodiment 2
1, a kind of 7-dehydrocholesterol preparation method comprises the steps:
1) esterification
SUV+Benzoyl chloride 99min. → cholesterol benzoate
Molar ratio of material: SUV: Benzoyl chloride 99min. 1:0.9
The synthetic of SUV benzene methyl carries out in two steps, and the one, Benzoyl chloride 99min. synthetic, the 2nd, be raw material synthetic cholesterol benzoic ether with Benzoyl chloride 99min. and SUV.Specific embodiments is following:
The sulfur oxychloride that newly steams is at room temperature reacted 1h (sulfur oxychloride and benzoic mol ratio are 1.05 ︰ 1) with phenylformic acid at 50 ± 5 ℃, be warmed up to 90 ℃ then, reaction 2h.Normal pressure steams excessive sulfur oxychloride, and decompression steams Benzoyl chloride 99min. again, as the raw material of next step reaction.
SUV is dissolved in the exsiccant benzene, adds pyridine ［ W
SUV() ︰ V g
Benzene() ︰ V ml
Pyridine(ml)=1 ︰ 4 ︰ 1 ］, add Benzoyl chloride 99min. again, at room temperature reacted 15 minutes, slowly heating is warming up to 90 ℃, esterification 10h under this temperature then; The cooling back adds and benzene equal-volume 1NHCl solution, tells organic layer, and water layer is with anhydrous diethyl ether extraction three times.Merge organic layer and ether extraction liquid, behind anhydrous magnesium sulfate drying, boil off organic solvents such as ether, benzene, separate out thick product after the cooling.With absolute ethyl alcohol recrystallization 2-3 time, obtain white crystal, i.e. cholesterol benzoate.
2) bromination reaction: cholesterol benzoate+NBS → 7-bromo cholesterol benzoate molar ratio of material: cholesterol benzoate: NBS 1:0.9
Logical nitrogen protection in the reaction kettle, tetracol phenixin is made solvent, adds cholesterol benzoate, is heated to 78
℃, gradation adds NBS, adds a little Diisopropyl azodicarboxylate and makees initiator, and reaction 3h filters, and washes with ethanol, promptly gets 7-bromo cholesterol benzoate.
3) remove bromination reaction
7-bromo cholesterol benzoate+pyridine → 7-dehydrocholesterol benzoate
Molar ratio of material: 7-bromo cholesterol benzoate: pyridine 1:1.0
7-bromo cholesterol benzoate and pyridine react in ethanol and generate 7-dehydrocholesterol benzoate, and after the optimization, the reaction times is 2h, and temperature is 85 ℃, gets 7-dehydrocholesterol benzoate.
4) hydrolysis saponification reaction
7-dehydrocholesterol benzoate+Pottasium Hydroxide → 7-dehydrocholesterol
Molar ratio of material: 7-dehydrocholesterol benzoic ether: Pottasium Hydroxide 1:1.0
7-dehydrocholesterol benzoate and Pottasium Hydroxide react in ethanol and generate the 7-dehydrocholesterol, and the reaction times is 2h, and temperature is 80 ℃, get the 7-dehydrocholesterol.Embodiment 3
1, a kind of 7-dehydrocholesterol preparation method comprises the steps:
1) esterification
SUV+Benzoyl chloride 99min. → cholesterol benzoate
Molar ratio of material: SUV: Benzoyl chloride 99min. 1:1.9
The synthetic of SUV benzene methyl carries out in two steps, and the one, Benzoyl chloride 99min. synthetic, the 2nd, be raw material synthetic cholesterol benzoic ether with Benzoyl chloride 99min. and SUV.Specific embodiments is following:
The sulfur oxychloride that newly steams is at room temperature reacted 1h (sulfur oxychloride and benzoic mol ratio are 1.05 ︰ 1) with phenylformic acid at 50 ± 5 ℃, be warmed up to 90 ℃ then, reaction 2h.Normal pressure steams excessive sulfur oxychloride, and decompression steams Benzoyl chloride 99min. again, as the raw material of next step reaction.
SUV is dissolved in the exsiccant benzene, adds pyridine ［ W
SUV() ︰ V g
Benzene() ︰ V ml
Pyridine(ml)=1 ︰ 4 ︰ 1 ］, add Benzoyl chloride 99min. again, at room temperature reacted 15 minutes, slowly heating is warming up to 105 ℃, esterification 6h under this temperature then; The cooling back adds and benzene equal-volume 1NHCl solution, tells organic layer, and water layer is with anhydrous diethyl ether extraction three times.Merge organic layer and ether extraction liquid, behind anhydrous magnesium sulfate drying, boil off organic solvents such as ether, benzene, separate out thick product after the cooling.With absolute ethyl alcohol recrystallization 2-3 time, obtain white crystal, i.e. cholesterol benzoate.
2) bromination reaction: cholesterol benzoate+NBS → 7-bromo cholesterol benzoate molar ratio of material: cholesterol benzoate: NBS 1:1.6
Logical nitrogen protection in the reaction kettle, tetracol phenixin is made solvent, adds cholesterol benzoate, is heated to 90
℃, gradation adds NBS, adds a little Diisopropyl azodicarboxylate and makees initiator, and reaction 6h filters, and washes with ethanol, promptly gets 7-bromo cholesterol benzoate.
3) remove bromination reaction
7-bromo cholesterol benzoate+pyridine → 7-dehydrocholesterol benzoate
Molar ratio of material: 7-bromo cholesterol benzoate: pyridine 1:1.7
7-bromo cholesterol benzoate and pyridine react in ethanol and generate 7-dehydrocholesterol benzoate, and after the optimization, the reaction times is 4h, and temperature is 65 ℃, gets 7-dehydrocholesterol benzoate.
4) hydrolysis saponification reaction
7-dehydrocholesterol benzoate+Pottasium Hydroxide → 7-dehydrocholesterol
Molar ratio of material: 7-dehydrocholesterol benzoic ether: Pottasium Hydroxide 1:1.9
7-dehydrocholesterol benzoate and Pottasium Hydroxide react in ethanol and generate the 7-dehydrocholesterol, and the reaction times is 4h, and temperature is 60 ℃, get the 7-dehydrocholesterol.
Through innovative technology, the yield of target product has reached 60%, has improved 10% than the yield of other producers 50%.Product content has reached 98%, has improved 3% than existing technology content 95%.For society provides the fine vitamin raw materials, tangible economic and social benefit is arranged.
All simple distortion of under the situation that does not break away from core of the present invention, making or modification all fall into protection scope of the present invention.
Claims (6)
1. a 7-dehydrocholesterol preparation method is characterized in that: comprise the steps:
1) SUV and Benzoyl chloride 99min. are carried out esterification, make cholesterol benzoate;
2) cholesterol benzoate and bromide are positioned bromination reaction, make 7-bromo cholesterol benzoate;
3) 7-bromo cholesterol benzoate and pyridine are removed bromination reaction, make 7-dehydrocholesterol benzoic ether;
4) with 7-dehydrocholesterol benzoic ether and the Pottasium Hydroxide saponification reaction that is hydrolyzed, make title product 7-dehydrocholesterol.
2. 7-dehydrocholesterol preparation method according to claim 1 is characterized in that: the bromide of participating in bromination reaction said step 2) is a N-bromination succimide, is called for short NBS.
3. 7-dehydrocholesterol preparation method according to claim 1 is characterized in that: the molar ratio of material that carries out esterification in the said step 1) is: SUV: Benzoyl chloride 99min. 1:0.9-1:1.9, and the reaction times is 6-12h, temperature is 90-110 ℃.
4. 7-dehydrocholesterol preparation method according to claim 1; It is characterized in that: the molar ratio of material that carries out bromination reaction said step 2) is: cholesterol benzoate: N-bromination succimide 1:0.9-1:1.6; Reaction times is 2-6h, and temperature is 75-90 ℃.
5. 7-dehydrocholesterol preparation method according to claim 1; It is characterized in that: go the material ratio of bromination reaction to be in the said step 3): 7-bromo cholesterol benzoate: pyridine 1:1.0-1:1.7; Reaction times is 2-4h, and temperature is 65-85 ℃.
6. the preparation method of 7-dehydrocholesterol according to claim 1; It is characterized in that: the material ratio of the saponification reaction that is hydrolyzed in the said step 4) is: 7-dehydrocholesterol benzoic ether: Pottasium Hydroxide 1:1.0-1:1.9; Reaction times is 2-4h, and temperature is 60-80 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101630409A CN102702295A (en) | 2012-05-24 | 2012-05-24 | Preparation method of 7-dehydrocholesterol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101630409A CN102702295A (en) | 2012-05-24 | 2012-05-24 | Preparation method of 7-dehydrocholesterol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102702295A true CN102702295A (en) | 2012-10-03 |
Family
ID=46895388
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101630409A Pending CN102702295A (en) | 2012-05-24 | 2012-05-24 | Preparation method of 7-dehydrocholesterol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102702295A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104017042A (en) * | 2014-05-19 | 2014-09-03 | 河南利伟生物药业股份有限公司 | Separation purification method for 7-dehydrocholesterol |
| CN106496298A (en) * | 2016-08-31 | 2017-03-15 | 四川省玉鑫药业有限公司 | A kind of production method of 7 dehydrocholesterol |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220075A (en) * | 2008-01-25 | 2008-07-16 | 北京化工大学 | Preparation method for 7-dehydrochol esterol |
| CN101619089A (en) * | 2009-07-28 | 2010-01-06 | 陈大刚 | Anticancer drug CL168, synthesis method and application thereof |
| CN102030794A (en) * | 2010-12-01 | 2011-04-27 | 安徽丰原发酵技术工程研究有限公司 | Method for preparing 7-dehydrocholesterol |
| US20110207952A1 (en) * | 2010-02-22 | 2011-08-25 | Rafael Avila | Cholesterol extraction from algae and preparation of vegan vitamin d3 |
| CN102485739A (en) * | 2010-12-06 | 2012-06-06 | 薛家禄 | Novel synthesis technology of 7-dehydrocholesterol |
-
2012
- 2012-05-24 CN CN2012101630409A patent/CN102702295A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220075A (en) * | 2008-01-25 | 2008-07-16 | 北京化工大学 | Preparation method for 7-dehydrochol esterol |
| CN101619089A (en) * | 2009-07-28 | 2010-01-06 | 陈大刚 | Anticancer drug CL168, synthesis method and application thereof |
| US20110207952A1 (en) * | 2010-02-22 | 2011-08-25 | Rafael Avila | Cholesterol extraction from algae and preparation of vegan vitamin d3 |
| CN102030794A (en) * | 2010-12-01 | 2011-04-27 | 安徽丰原发酵技术工程研究有限公司 | Method for preparing 7-dehydrocholesterol |
| CN102485739A (en) * | 2010-12-06 | 2012-06-06 | 薛家禄 | Novel synthesis technology of 7-dehydrocholesterol |
Non-Patent Citations (1)
| Title |
|---|
| ANDRZEJ SLOMINSKI 等: "A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin", 《EUR. J. BIOCHEM.》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104017042A (en) * | 2014-05-19 | 2014-09-03 | 河南利伟生物药业股份有限公司 | Separation purification method for 7-dehydrocholesterol |
| CN104017042B (en) * | 2014-05-19 | 2016-01-06 | 河南利伟生物药业股份有限公司 | A kind of separation purification method of 7-DHC |
| CN106496298A (en) * | 2016-08-31 | 2017-03-15 | 四川省玉鑫药业有限公司 | A kind of production method of 7 dehydrocholesterol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104744237B (en) | A kind of 2-(4-2-bromomethylphenyl) propanoic acid preparation method | |
| CN106699774A (en) | Sulbactam sodium preparation method | |
| CN103005160A (en) | Compound acidifier for feed, and preparation method and application of acidifier | |
| CN101948402A (en) | Method for preparing D-calcium pantothenate | |
| CN102702295A (en) | Preparation method of 7-dehydrocholesterol | |
| CN102030794B (en) | Method for preparing 7-dehydrocholesterol | |
| CN103238561B (en) | A kind of method for raising pigs | |
| CN103181502B (en) | Efficient mineral nutritional feed additive for promoting growth and development of goat after weaning | |
| CN102267918B (en) | Method for preparing betaine hydrochloride | |
| CN111011620A (en) | Cow rumen sustained-release calcium preparation and preparation method thereof | |
| CN102485739A (en) | Novel synthesis technology of 7-dehydrocholesterol | |
| CN103651770B (en) | Green pepper antistaling agent and preparation method thereof | |
| CN103113312B (en) | Quinocetone derivative and preparation method and application thereof | |
| CN104672155B (en) | A kind of synthetic method for improving quinocetone | |
| CN102464642B (en) | Compound, preparation method thereof and application thereof as feed additive | |
| CN102452932B (en) | Preparation method for L-(+)-tartaric acid | |
| CN102461666A (en) | Production method of water-soluble dietary fibre milk beverage | |
| CN108017534A (en) | A kind of method for preparing sodium Diacetate | |
| CN102948609B (en) | Method for preparing modified amino acid chelated iron feed additive | |
| CN103766615B (en) | A kind of method of feedstuff mildew | |
| CN204237778U (en) | A kind of new device producing L-Trp with enzyme process binding film technology | |
| CN102415959A (en) | Whitening vanishing cream | |
| CN102726630B (en) | Feed additive for beautifying fur of raccoon dog | |
| KR101872770B1 (en) | Composition for preventing or treating cancer comprising novel selenobenzene compound | |
| CN106905131B (en) | Synthesis method of beta-menadione |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20121003 |