CN108484710A - A kind of content of beary metal control method of 7-Keto DHEAAc - Google Patents
A kind of content of beary metal control method of 7-Keto DHEAAc Download PDFInfo
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- CN108484710A CN108484710A CN201810231666.6A CN201810231666A CN108484710A CN 108484710 A CN108484710 A CN 108484710A CN 201810231666 A CN201810231666 A CN 201810231666A CN 108484710 A CN108484710 A CN 108484710A
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- keto
- added
- dheaac
- method described
- sodium chromate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0059—Estrane derivatives substituted in position 17 by a keto group
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Abstract
The invention discloses a kind of content of beary metal control methods of 7 ketone group trans-Dehydrorosterone acetate, including Dehydroepiandrosterone Acetate and sodium chromate are carried out oxidation reaction, by oxidation reaction product elutriation, centrifuge washing obtains the crude product containing 7 ketone group trans-Dehydrorosterone acetates；Heavy metal chelant is added in the crude product containing 7 ketone group trans-Dehydrorosterone acetates to be dissolved by heating, lysate is filtered, is crystallized, centrifugal drying, which obtains, contains 7 ketone group trans-Dehydrorosterone acetate crystallized products.For the method for the present invention without conditions such as stringent high temperature, high vacuum, equipment requirement is low, process control is simple, can reduce the dosage of sodium chromate, can effectively reduce content of beary metal in 7 ketone group trans-Dehydrorosterone acetates, improves yield rate.
Description
Technical field
The invention belongs to chemical industry synthesis field more particularly to a kind of content of beary metal controlling parties of 7-keto-dehydroepiandrosterone
Method.
Background technology
7-Keto DHEAAc energy anti-aging, strengthen immunity can also improve brain function, enhancing memory
Power prevents senile dementia, stimulates liver organized enzyme, the metabolism of especially hot enzyme, but also with fat is reduced, maintain regular
Matter index increases bone and the functions such as muscle density and vigor.2.5 times of its physiological activity ratio DHEA high, and will not generation in human body
It thanks as sex hormone, has no toxic side effect, take safely and effectively.Therefore nearly ten years people in 7-Keto DHEAAc
A large amount of research has been done in synthetic method.Using trans-Dehydrorosterone acetate in the building-up process of raw material, mainly to pass through alkene
Third selective oxidation synthesizes 7-Keto DHEAAc.
The production technology of existing 7-Keto DHEAAc includes：Using chromium trioxide as the synthesis side of oxidant
Method, using tertbutanol peroxide as the synthetic method of oxidant, using sodium chromate as the synthetic method of oxidant.Wherein, with three oxidations
Chromium is the synthetic method, relatively low as the synthetic method yield rate of oxidant using tertbutanol peroxide of oxidant, does not have economic meaning
Justice；It is more common by the synthetic method of oxidant of sodium chromate, but sodium chromate dosage is big, and part finished product content of beary metal does not reach
Mark, and sewage disposal expense is high.
Invention content
The purpose of the present invention is being directed to the above shortcoming, a kind of heavy metal of 7-Keto DHEAAc is provided
Content control method, solves that current sodium chromate dosage is big, part finished product content of beary metal problem not up to standard.
In the first aspect of the present invention, a kind of content of beary metal controlling party of 7-Keto DHEAAc is provided
Method, the method includes：
(1) Dehydroepiandrosterone Acetate and sodium chromate are subjected to oxidation reaction, by oxidation reaction product elutriation, centrifuge washing,
The crude product of 7-Keto DHEAAc must be contained.
(2) heavy metal chelant is added in (1) product to be dissolved by heating, lysate is filtered, crystallize, centrifugation is dry
Dry acquisition crystallized product containing 7-Keto DHEAAc.
In a preference, in step (1), the oxidation reaction includes：By 8 times of Dehydroepiandrosterone Acetate addition-
Sodium chromate, stirring, heat preservation 2 is added in 30 DEG C -40 DEG C (preferably 35 DEG C -40 DEG C) in the acetic acid of 10 times of (preferably 9 times) weight
Hour, obtain oxidation reaction product.
In another preference, the dosage of the sodium chromate is identical as Dehydroepiandrosterone Acetate.
In another preference, the elutriation process is as follows：Pure water is added in oxidation reaction product, stirs, is cooled to 0
℃-10℃。
In another preference, the centrifuge washing process is as follows：Clear water is sprayed in centrifuge, until pH>5.5
When, terminate washing.
In another preference, in step (2), the heating for dissolving process is as follows：Hydrogen meter will be gone male containing 7- ketone groups
The organic solvent of 3 times -5 times (preferably 4 times) weight is added in the crude product of ketone acetate, in 20 DEG C -40 DEG C (preferably 30 DEG C -40
DEG C) under heavy metal chelant is added, stir, be heated to 100 DEG C -120 DEG C, keep the temperature 2 hours, diatomite is added, at 40 DEG C -70 DEG C
(preferably 45 DEG C -75 DEG C) are kept the temperature, and filtering harvest filtrate is slowly cooled to 0 DEG C -10 DEG C, obtains 7-keto-dehydroepiandrosterone vinegar
Acid esters crystallizes.
In another preference, the organic solvent is selected from (but not limited to)：Ethyl alcohol, methanol, ethyl acetate, acetone.
In another preference, the heavy metal chelant dosage is the 0.005%-0.05% of organic solvent.
In another preference, the heavy metal chelant is selected from (but not limited to)：EDTA, DTPA, HBED.
Other aspects of the present invention are apparent to those skilled in the art due to this disclosure
's.
Compared with the prior art, the invention has the advantages that：
(1) present invention is by being added heavy metal chelant so that content of beary metal in 7-Keto DHEAAc
It substantially reduces, especially chromium content, in addition, lead content is smaller than 1.0PPm.
(2) present invention can reduce the use of sodium chromate by the solvent of preferred oxidation reaction, reaction temperature and raw material proportioning
Amount improves yield rate.
Specific implementation mode
The present inventor finds a kind of heavy metal control of 7-Keto DHEAAc by in-depth study repeatedly
Method processed.The method includes：
(1) Dehydroepiandrosterone Acetate and sodium chromate are subjected to oxidation reaction, by oxidation reaction product elutriation, centrifuge washing,
The crude product of 7-Keto DHEAAc must be contained.
(2) heavy metal chelant is added in (1) product to be dissolved by heating, lysate is filtered, crystallize, centrifugation is dry
Dry acquisition crystallized product containing 7-Keto DHEAAc.
In a preference, in step (1), the oxidation reaction includes：By 8 times of Dehydroepiandrosterone Acetate addition-
Sodium chromate, stirring, heat preservation 2 is added in 30 DEG C -40 DEG C (preferably 35 DEG C -40 DEG C) in the acetic acid of 10 times of (preferably 9 times) weight
Hour, obtain oxidation reaction product.
In another preference, the dosage of the sodium chromate is identical as Dehydroepiandrosterone Acetate.
In another preference, the elutriation process is as follows：Pure water is added in oxidation reaction product, stirs, is cooled to 0
℃-10℃。
In another preference, the centrifuge washing process is as follows：Clear water is sprayed in centrifuge, until pH>5.5
When, terminate washing.
In another preference, in step (2), the heating for dissolving process is as follows：Hydrogen meter will be gone male containing 7- ketone groups
The organic solvent of 3 times -5 times (preferably 4 times) weight is added in the crude product of ketone acetate, in 20 DEG C -40 DEG C (preferably 30 DEG C -40
DEG C) under heavy metal chelant is added, stir, be heated to 100 DEG C -120 DEG C, keep the temperature 2 hours, diatomite is added, at 40 DEG C -70 DEG C
(preferably 45 DEG C -75 DEG C) are kept the temperature, and filtering harvest filtrate is slowly cooled to 0 DEG C -10 DEG C, obtains 7-keto-dehydroepiandrosterone vinegar
Acid esters crystallizes.
In another preference, the organic solvent is selected from (but not limited to)：Ethyl alcohol, methanol, ethyl acetate, acetone.
In another preference, the heavy metal chelant dosage is the 0.005%-0.05% of organic solvent.
In another preference, the heavy metal chelant is selected from (but not limited to)：EDTA, DTPA, HBED.
For the method for the invention without conditions such as stringent high temperature, high vacuum, equipment requirement is low, process control is simple, obtains
The product content of beary metal obtained is low, and yield rate is higher.
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
And it does not limit the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to normal condition, or
According to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise percentage and number are calculated by weight.
Unless otherwise defined, all professions used in text are used to anticipate with known to one skilled in the art with science
Justice is identical.In addition, any method and material similar or impartial to described content all can be applied in the present invention.It is described in text
Preferred implement methods and materials be for illustrative purposes only.
When embodiment 1, Dehydroepiandrosterone Acetate and sodium chromate carry out oxidation reaction in different solvents, the dosage of sodium chromate
Research
In proportioning：Trans-Dehydrorosterone acetate 100kg, solvent dosage 900kg are examined under the conditions of controlling 30 DEG C -35 DEG C of temperature
Different solvents have been examined, it is found that oxidation needs sodium chromate, methanol ＞ acetonitrile ＞ aceticanhydride ＞ acetic acid in different solvents.
| Solvent | Need sodium chromate (kg) |
| Methanol | 200 |
| Acetonitrile | 160 |
| Aceticanhydride | 140 |
| Acetic acid | 110 |
When embodiment 2, Dehydroepiandrosterone Acetate and sodium chromate carry out oxidation reaction at different temperatures, the dosage of sodium chromate
Research
In proportioning：Trans-Dehydrorosterone acetate 100kg, acetic acid 900kg, investigating different temperatures oxidation needs sodium chromate：Temperature
It is higher to need sodium chromate fewer.Oxidation is heat release, will be lost control of if temperature surpasses 50 DEG C, so highest is set to 40 DEG C.
| Oxidizing temperature DEG C | Need sodium chromate (Kg) |
| 30-35 | 110 |
| 35-40 | 100 |
Embodiment 3, heavy metal chelant are to the shadow of content of beary metal in 7-Keto DHEAAc crystallized product
It rings
1. being added without heavy metal chelant
The crude product 100kg containing 7-Keto DHEAAc, ethyl alcohol 400kg are added in refining kettle, stirring adds
Heat keeps the temperature 2 hours to 100 DEG C -120 DEG C, and diatomite is added, and in 40 DEG C of -70 DEG C of heat preservations, filtering harvest filtrate is slowly cooled to 0
DEG C -10 DEG C, obtain 7-Keto DHEAAc crystallization.
2. heavy metal chelant is added
In refining kettle be added the crude product 100kg containing 7-Keto DHEAAc, ethyl alcohol 400kg, in 20 DEG C-
Heavy metal chelant is added at 40 DEG C, stirs, is heated to 100 DEG C -120 DEG C, keeps the temperature 2 hours, diatomite is added, at 40 DEG C -70
DEG C heat preservation, filtering harvest filtrate are slowly cooled to 0 DEG C -10 DEG C, obtain 7-Keto DHEAAc crystallization.
3. the comparison of lead content in crystallized product
| Heavy metal chelant | Lead content in crystallized product |
| It is not added | 1.5PPm |
| It is added | 0.6PPm |
It can be seen that the dosage of sodium chromate can be reduced by optimizing solvent, reaction temperature and the raw material proportioning of oxidation reaction, it is added
Heavy metal chelant can control the lead content in final product to be less than 1.0ppm, effectively reduce content of beary metal, improve yield rate.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document
It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can
To be made various changes or modifications to the present invention, such equivalent forms equally fall within model defined by the application the appended claims
It encloses.
Claims (8)
1. a kind of content of beary metal control method of 7-Keto DHEAAc, which is characterized in that the method includes：
（1）Dehydroepiandrosterone Acetate and sodium chromate are subjected to oxidation reaction, by oxidation reaction product elutriation, centrifuge washing must contain
The crude product of 7-Keto DHEAAc；
（2）Heavy metal chelant is added in the crude product containing 7-Keto DHEAAc to be dissolved by heating, will dissolve
Product filters, and crystallization, centrifugal drying obtains crystallized product containing 7-Keto DHEAAc.
2. according to the method described in claim 1, it is characterized in that, step（1）In, the oxidation reaction includes：Acetic acid is gone
The acetic acid of 8 times of -10 times of weight is added in hydrogen meter androsterone, and in 30 DEG C -40 DEG C, sodium chromate is added, and stirring keeps the temperature 2 hours, must aoxidize anti-
Answer product.
3. according to the method described in claim 1, it is characterized in that, the dosage of the sodium chromate and Dehydroepiandrosterone Acetate phase
Together.
4. according to the method described in claim 1, it is characterized in that, step（1）In, the elutriation process is as follows：It will aoxidize anti-
Answer product that pure water is added, stirring is cooled to 0 DEG C -10 DEG C.
5. according to the method described in claim 1, it is characterized in that, step（2）In, the heating for dissolving process is as follows：It will contain
There is the crude product of 7-Keto DHEAAc that the organic solvent of 3 times of -5 times of weight is added, a huge sum of money is added at 20 DEG C -40 DEG C
Belong to chelating agent, stirring is heated to 100 DEG C -120 DEG C, keeps the temperature 2 hours, and diatomite is added, in 40 DEG C of -70 DEG C of heat preservations, filtering harvest
Filtrate is slowly cooled to 0 DEG C -10 DEG C, obtains 7-Keto DHEAAc crystallization.
6. according to the method described in claim 4, it is characterized in that, the organic solvent is selected from：Ethyl alcohol, methanol, ethyl acetate,
Acetone.
7. according to the method described in claim 1, which is characterized in that the heavy metal chelant dosage is organic solvent
0.005%-0.05%。
8. according to the method described in claim 1, which is characterized in that the heavy metal chelant is selected from：EDTA, DTPA,
HBED。
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810231666.6A CN108484710A (en) | 2018-03-20 | 2018-03-20 | A kind of content of beary metal control method of 7-Keto DHEAAc |
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| CN201810231666.6A CN108484710A (en) | 2018-03-20 | 2018-03-20 | A kind of content of beary metal control method of 7-Keto DHEAAc |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6274746B1 (en) * | 2000-08-30 | 2001-08-14 | Padma Marwah | Process for allylic oxidation using metal hypochlorite and alkyl hydroperoxide |
| CN1814615A (en) * | 2006-03-02 | 2006-08-09 | 云南大学 | 7-keto deoxy epiandrosterone and its acetate synthesizing method |
| CN101505771A (en) * | 2006-08-17 | 2009-08-12 | 荷兰联合利华有限公司 | Processes for production of HOODIA plant extracts containing steroidal glycosides |
-
2018
- 2018-03-20 CN CN201810231666.6A patent/CN108484710A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6274746B1 (en) * | 2000-08-30 | 2001-08-14 | Padma Marwah | Process for allylic oxidation using metal hypochlorite and alkyl hydroperoxide |
| CN1814615A (en) * | 2006-03-02 | 2006-08-09 | 云南大学 | 7-keto deoxy epiandrosterone and its acetate synthesizing method |
| CN101505771A (en) * | 2006-08-17 | 2009-08-12 | 荷兰联合利华有限公司 | Processes for production of HOODIA plant extracts containing steroidal glycosides |
Non-Patent Citations (3)
| Title |
|---|
| KAGAN, HENRI B. 等: "Inverted steroids. IV. First approximation of an "inverted" cortisone", 《BULLETIN DE LA SOCIETE CHIMIQUE DE FRANCE》 * |
| 苏会东 等主编: "《水污染控制工程》", 31 May 2017 * |
| 黄平 等: "薯蓣皂素下游产品7-酮基去氢表雄酮醋酸酯合成进展", 《广东化工》 * |
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