CN109456206A - A kind of recovery method of right amine - Google Patents
A kind of recovery method of right amine Download PDFInfo
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- CN109456206A CN109456206A CN201811528471.4A CN201811528471A CN109456206A CN 109456206 A CN109456206 A CN 109456206A CN 201811528471 A CN201811528471 A CN 201811528471A CN 109456206 A CN109456206 A CN 109456206A
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- right amine
- recovery method
- hydroxide solution
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention belongs to the technical fields of biotin synthesis, it is related to a kind of recovery method of right amine of biotin raw material, described method includes following steps: (1) taking lactone hydrolyzate, organic solvent is added and extracts lactone, isolates the water layer containing right amine hydrochlorate；(2) alkali is added in water layer and adjusts pH value to 5-7, viscous brown object is precipitated after stirring, filtering obtains filtrate；(3) alkali is added in the filtrate of step (2) and further adjusts pH value to 12-13, right amine crude product is precipitated after stirring, after filtering out above-mentioned right amine crude product；(4) right amine crude product is eluted with water, right amine is obtained after drying.The present invention provides a kind of method for recycling right amine from lactone hydrolyzate, this method is simple, efficient, adaptable.
Description
Technical field
The invention belongs to the technical fields of biotin synthesis, are related to a kind of recovery method of right amine of biotin raw material.
Background technique
Biotin also known as biotin, vitamin B7, biotin belong to water-soluble (vitamin) B race, are that dimension needed by human is raw
One of Major Members in plain race.Biotin is a weight in the coenzyme and protein and fatty intermediate supersession of invertase
Coenzyme is wanted, humans and animals normal growth and development, protection skin, feather and bone-marrow-healthy is being maintained to play essential effect.
Thus medical treatment, multidimensional preparation and in terms of be widely applied.Entitled (3aS, 4S, the 6aR)-hexahydro-of its chemistry
The positive valeric acid of 2- oxo -1H- thiophene [3,4-d] imidazoles -4-, structure is as shown in following formula I:
Simultaneously [3,4-d] imidazoles -2.4 (1H)-diketone is (hereinafter referred to as (3aS, 6aR) -1.3- dibenzyl-tetrahydro -4H- furans
Lactone) it is one of biotin synthesis key intermediate, and (1S.2S)-(+)-Su Shi -1- (p-nitrophenyl) -2- amino -
1.3- propylene glycol (hereinafter referred to as right amine) is the raw material for synthesizing lactone.
The industrializing synthesis route of biotin is essentially all using the sternbach route by improvement at present.I.e. from
Naphthenic acid sets out, and is first condensed with right amine, then reductive hydrolysis desymmetrization generation lactone, then it is thio, connect side chain, then hydrogen
Change, debenzylation, cyclization generate biotin.Naphthenic acid and right amine (by-product in production of chloramphenicol, with chirality), which generate, has light
Learn active cyclic amides.The difference of steric environment locating for two carbonyls in cyclic amides molecule, therefore can be diastereomeric
It is selectively reduced into diastereoisomer, then obtains lactone.
The chemical equation of interior Lipase absobed is as follows:
The process requirement largely uses right amine.Right amine is the by-product during synthesizing chloramphenicol.As chloramphenicol is complete
The gradually disabling of ball range, supply falls short of demand in the market, and price climbs up and up.And work as in the hydrolyzate of lactone containing a large amount of right amine
It is exhausted as waste material, huge economic value is not only caused to waste, but also pollute environment, increase environmental protection of enterprise pressure.How to recycle
The great economic value of right amine and the value of environmental protection in lactone hydrolyzate.
Chinese patent literature CN107382752A discloses a kind of method of the right amine of raw material of recycling production D-biotin, packet
It includes following steps: (1) content of right amine in the lactone mother liquor generated when preparing lactone using right amine method is first detected, then by lactone
Mother liquor is at the uniform velocity cooled to temperature a, is precipitated after boric acid through filtrate is obtained by filtration；(2) filtrate is removed into water by evaporated under reduced pressure, be added molten
Agent is heated to reflux, then is at the uniform velocity cooled under certain temperature t and then is crystallized, filter；(3) filtrate is at the uniform velocity cooled to certain temperature again
Right amine hydrochlorate crude product is obtained by filtration in q；(4) right amine hydrochlorate crude product is dissolved with water, is heated to dissolved clarification, is added after dissolved clarification
Adjusting PH with base=9~10, then it is at the uniform velocity cooled to certain temperature p, it is washed after keeping the temperature filtering at least one hour, obtains right amine wet product,
Drying obtains right amine finished product.
However right amine is recycled according to mode described in its, and it always will appear a large amount of viscous brown objects when every time plus alkali is precipitated, it can not
Right amine is successfully obtained, the reason is that there is the by-product of large amount of complex to generate in the reduction process of previous step, disturbs right amine
Precipitation.Therefore this method has very high request to the purity of raw material, is not suitable for the demand of industrialized production.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of method that right amine is recycled from lactone hydrolyzate, the party
Method is simple, efficient, adaptable.
Specifically, right amine recovery method of the invention, includes the following steps:
(1) lactone hydrolyzate is taken, organic solvent is added and extracts lactone, isolates the water layer containing right amine hydrochlorate；
(2) alkali is added in water layer and adjusts pH value to 5-7, viscous brown object is precipitated after stirring, filtering obtains filtrate；
(3) alkali is added in the filtrate of step (2) and further adjusts pH value to 12-13, right amine crude product is precipitated after stirring, then
Filter out above-mentioned right amine crude product；
(4) right amine crude product is eluted with water, right amine is obtained after drying.
Above-mentioned lactone hydrolyzate is prepared using known method, i.e., carries out condensation reaction using naphthenic acid and right amine, then carry out
Reduction reaction and hydrolysis obtain lactone hydrolyzate.
Organic solvent in above-mentioned steps (1) is selected from ethyl acetate, methylene chloride, toluene, one of dimethylbenzene.
Alkali in above-mentioned steps (2) and step (3) is selected from sodium hydroxide solution or potassium hydroxide solution.
Above-mentioned sodium hydroxide solution is preferably 30% sodium hydroxide solution, and the potassium hydroxide solution is preferably 30% hydrogen-oxygen
Change potassium solution.
The stirring of above-mentioned steps (2), whipping temp are room temperature, and mixing time is 0.5-5 hours.
The stirring of above-mentioned steps (3), whipping temp are room temperature, and mixing time is 0.5-5 hours.
Filter type in above-mentioned steps (2) is to filter.
The improvement of the present invention compared with the existing technology is as follows:
The present invention is separated the impurity for including in right amine hydrochlorate, success by adjusting pH value stage by stage twice
Recycle right amine.This method is simple, efficient, and the right amine of high-purity can be recycled out from the lactone hydrolyzate of complicated component, is had
Very big industrialized utilization value.The right amine purity recycled through the invention can achieve 97.5% or more, and yield is (with reduction
Object is starting material calculating) it can achieve 85% or more.
Specific embodiment
Below by the description of specific embodiment, the invention will be further described, but it is to limit of the invention that this, which is not,
System, those skilled in the art's basic thought according to the present invention, various modifications may be made or improves, but without departing from
Basic thought of the invention, is all within the scope of the present invention.
Various raw materials and reagents used in the embodiment of the present invention are commercially available purchase unless otherwise instructed.
The detection method of moderate purity of the embodiment of the present invention uses high performance liquid chromatography.Detection device uses Shimadzu LC-16.
Embodiment 1: the preparation of reduzate.
45 grams of naphthenic acid (0.127mol), 26.9 grams of right amine (0.127mol), toluene 500ml, pyridine are added in reaction flask
50ml, solvent evaporated is reduzate after being heated to reflux 3 hours.
Embodiment 2
10.7 grams of reduzate (0.02mol) are taken, 20% hydrochloric acid 100ml is added, is heated to reflux under stirring 2 hours, cools down, adds
Entering 100ml methylene chloride, split-phase, layer of fetching water adjusts pH=6.5 with 30% sodium hydroxide solution, stirs 0.5 hour at room temperature,
A large amount of viscous brown objects are precipitated, filter, 30% sodium hydroxide solution is added in filtrate and adjusts pH=12.0, it is solid that a large amount of whites are precipitated
Body stirs 0.5 hour at room temperature, and filtering, filter cake dries to obtain 3.61 grams of right amine after being eluted with water.By detect purity is
98.2%, yield 85.1%.
Embodiment 3
32.1 grams of reduzate (0.06mol) are taken, 20% hydrochloric acid 100ml is added, is heated to reflux under stirring 2 hours, cools down, adds
Entering 100ml ethyl acetate, split-phase, layer of fetching water adjusts pH=7.0 with 30% potassium hydroxide solution, stirs 2.5 hours at room temperature,
A large amount of viscous brown objects are precipitated, filter, filtrate is added 30% potassium hydroxide solution and adjusts pH=12.5, and it is solid that a large amount of whites are precipitated
Body stirs 2.5 hours at room temperature, and filtering, filter cake dries to obtain 11.1 grams of right amine after being eluted with water.By detect purity is
98.5%, yield 87.2%.
Embodiment 4
53.5 grams of reduzate (0.1mol) are taken, 20% hydrochloric acid 500ml is added, is heated to reflux under stirring 2 hours, cools down, adds
Enter 500ml dimethylbenzene, split-phase, layer of fetching water adjusts pH=5.0 with 30% sodium hydroxide solution, stirs 5 hours at room temperature, is precipitated
A large amount of viscous brown objects, filter, and filtrate is added 30% sodium hydroxide solution and adjusts pH=13.0, and a large amount of white solids, room is precipitated
Temperature lower stirring 5 hours, filtering, filter cake dried to obtain 18.4 grams of right amine after being eluted with water.By detect purity be 97.8%, yield
It is 86.8%.
Claims (7)
1. a kind of recovery method of right amine, which is characterized in that described method includes following steps:
(1) lactone hydrolyzate is taken, organic solvent is added and extracts lactone, isolates the water layer containing right amine hydrochlorate；
(2) alkali is added in water layer and adjusts pH value to 5-7, viscous brown object is precipitated after stirring, filtering obtains filtrate；
(3) alkali is added in the filtrate of step (2) and further adjusts pH value to 12-13, right amine crude product is precipitated after stirring, refilters
Above-mentioned right amine crude product out；
(4) right amine crude product is eluted with water, right amine is obtained after drying.
2. a kind of recovery method of right amine according to claim 1, which is characterized in that organic molten in the step (1)
Agent is selected from ethyl acetate, methylene chloride, toluene, one of dimethylbenzene.
3. a kind of recovery method of right amine according to claim 1, which is characterized in that in the step (2) and step (3)
Alkali be selected from sodium hydroxide solution or potassium hydroxide solution.
4. a kind of recovery method of right amine according to claim 3, which is characterized in that the sodium hydroxide solution is preferably
30% sodium hydroxide solution, the potassium hydroxide solution are preferably 30% potassium hydroxide solution.
5. a kind of recovery method of right amine according to claim 1, which is characterized in that the stirring of the step (2) is stirred
Mixing temperature is room temperature, and mixing time is 0.5-5 hours.
6. a kind of recovery method of right amine according to claim 1, which is characterized in that the stirring of the step (3) is stirred
Mixing temperature is room temperature, and mixing time is 0.5-5 hours.
7. a kind of recovery method of right amine according to claim 1, which is characterized in that the filtering side in the step (2)
Formula is to filter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811528471.4A CN109456206B (en) | 2018-12-13 | 2018-12-13 | Method for recovering dextroamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811528471.4A CN109456206B (en) | 2018-12-13 | 2018-12-13 | Method for recovering dextroamine |
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| CN109456206A true CN109456206A (en) | 2019-03-12 |
| CN109456206B CN109456206B (en) | 2021-11-02 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1266847A (en) * | 2000-01-27 | 2000-09-20 | 武汉大学 | Process for preparing ketone condensate of L-(+)-2-amino-1-p-nitrophenyl-1,3-propanediol |
| CN102491908A (en) * | 2011-12-16 | 2012-06-13 | 华东理工大学 | Method for recovering raw material chiral amine in waste water produced in biotin production process |
| CN107382752A (en) * | 2017-07-12 | 2017-11-24 | 杭州科兴生物化工有限公司 | A kind of method for reclaiming the right amine of raw material for making d biotins |
-
2018
- 2018-12-13 CN CN201811528471.4A patent/CN109456206B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1266847A (en) * | 2000-01-27 | 2000-09-20 | 武汉大学 | Process for preparing ketone condensate of L-(+)-2-amino-1-p-nitrophenyl-1,3-propanediol |
| CN102491908A (en) * | 2011-12-16 | 2012-06-13 | 华东理工大学 | Method for recovering raw material chiral amine in waste water produced in biotin production process |
| CN107382752A (en) * | 2017-07-12 | 2017-11-24 | 杭州科兴生物化工有限公司 | A kind of method for reclaiming the right amine of raw material for making d biotins |
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