CN109942426A - A kind of S-(-) processing method that recycles of-lipoic acid - Google Patents
A kind of S-(-) processing method that recycles of-lipoic acid Download PDFInfo
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- CN109942426A CN109942426A CN201910262491.XA CN201910262491A CN109942426A CN 109942426 A CN109942426 A CN 109942426A CN 201910262491 A CN201910262491 A CN 201910262491A CN 109942426 A CN109942426 A CN 109942426A
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- lipoic acid
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Abstract
The invention discloses a kind of processing methods that S- (-)-lipoic acid recycles, the following steps are included: S- (-)-lipoic acid is dissolved in organic solvent by (1), then alkali is added and carries out basification, obtains S- (-)-lipoic acid reaction solution；(2) S- (-)-lipoic acid reaction solution is subjected to Air Exposure, then carries out acidification and obtains yellow paste；(3) the yellow paste is dissolved in organic solvent, after thionyl chloride progress chlorination is added, ethyl alcohol is added and continues esterification, obtains 6,8-dichloro-octanoic acid ethyl ester.The present invention realizes S- (-)-lipoic acid and recycles, obtain the raw material 6 of synthesis alpha-lipoic acid, 8 dicloro caprylate ethyl esters, not only solve S- (-)-lipoic acid recycling problem, avoid material waste, and the cost of material of synthesis r-lipoic acid is considerably reduced, new approach is provided for industrial production r-lipoic acid.
Description
Technical field
The present invention relates to the processing sides that technical field of chemical synthesis more particularly to a kind of S- (-)-lipoic acid recycle
Method.
Background technique
Lipoic acid (alphalipoic acid) is a kind of coenzyme for being present in mitochondria, and similar vitamin can be eliminated and be led
Cause accelerated ageing and pathogenic free radical.Lipoic acid in vivo after intestinal absorption enter cell, have both it is fat-soluble with it is water-soluble
Characteristic, therefore can go everywhere without any hindrance here in whole body, reach any one cell area, provide human body comprehensive efficiency, be tool liposoluble
Property with water-soluble universal antioxidant.Wherein, what research found that lipoic acid plays a major role is r-lipoic acid part.Therefore,
R-lipoic acid study on the synthesis, for promoting r-lipoic acid to realize, industrialized production is of great significance.
With deepening continuously for the Study of synthesis method for synthesizing r-lipoic acid, by different raw starting materials, it was found that more
The method that kind realizes synthesis r-lipoic acid.Current main method for splitting has:
1, it uses adipic acid for starting material, after multistep synthesizes, synthesizes 6- hydroxyl -8 in 6- carbonyl -8- Lipase Catalyzed Resolution of Racemic Ethyl
When Lipase Catalyzed Resolution of Racemic Ethyl step, asymmetric syntheses is carried out as catalyst for object using Ru, the process of fractionation is omitted, simplifies work
Skill step.But not high, industrial mass production that there is product purities is difficult to the disadvantages of repeating.
2, after using the hydrolysis of 6,8-dichloro-octanoic acid ethyl ester, 6,8-dichloro-octanoic acid is higher through S- phenyl ethylamine fractionation acquisition purity
R-6,8- dicloro caprylate, but in addition the S-6 of half, 8- dicloro caprylate can not reuse.
3, use alpha-lipoic acid for raw material, with toluene etc. for solvent, Chiral Amine selected to be split, yield and purity compared with
Ideal, but after the completion of fractionation, it is larger that S- (-)-lipoic acid of the other half of residue of mother recycles difficulty.The prior art uses
Under conditions of high temperature, high pressure and nitrogen protection, so that the S- (-) of a part-lipoic acid completes racemization, but this process item
Part is harsh and easily lipoic acid is caused to polymerize.
Summary of the invention
It is an object of the invention to overcome the deficiencies of the prior art and provide a kind of processing that S- (-)-lipoic acid recycles
Method uses basification first, then through aeration, chloro, esterification treatment, obtains splitting raw material alpha-lipoic acid for synthesizing
Intermediate product 6,8-dichloro-octanoic acid ethyl ester is r-lipoic acid while effectively solution S- (-)-lipoic acid recycles problem
Synthesis provides new approach.
The purpose of the present invention is achieved by the following technical programs:
The processing method that a kind of S- (-)-lipoic acid provided by the invention recycles, comprising the following steps:
(1) S- (-)-lipoic acid is dissolved in organic solvent, alkali is then added and carries out basification, obtains S- (-)-sulphur
Sad reaction solution；
(2) S- (-)-lipoic acid reaction solution is subjected to Air Exposure, then carries out acidification and obtains yellow cream
Shape object；
(3) the yellow paste is dissolved in organic solvent, after thionyl chloride progress chlorination is added, second is added
Alcohol continues esterification, obtains 6,8-dichloro-octanoic acid ethyl ester.
Further, alkali concentration is 20~40% in step (1) of the present invention, according to molar ratio S- (-)-lipoic acid:
Alkali=1: 1.2~2.0；The temperature of basification is 40~50 DEG C, and the reaction time is 6~9h.
Further, the Air Exposure time is 2~4h in step (2) of the present invention；Acid concentration is 5~10%, 0~
Acidification is carried out at a temperature of 5 DEG C, until solution ph is 2~4.
Further, according to molar ratio S- (-)-lipoic acid in step (3) of the present invention: thionyl chloride=1: 1.0~
1.5；The temperature of chlorination is 40~60 DEG C, and the reaction time is 2~5h；According to molar ratio S- (-)-lipoic acid: ethyl alcohol=1:
2.0~3.5, the temperature of esterification is 0~20 DEG C, and the reaction time is 3~6h.
In above scheme, organic solvent of the present invention is toluene, ethyl acetate, t-butyl methyl ether.The alkali is hydrogen-oxygen
Change sodium, potassium hydroxide, calcium hydroxide.The acid is hydrochloric acid, sulfuric acid, acetic acid.
The invention has the following advantages:
(1) S- (-)-lipoic acid of the present invention realizes S- (-)-lipoic acid and follows through alkalization, aeration, chloro, esterification treatment
Ring utilizes, and obtains 6, the 8 dicloro caprylate ethyl ester of raw material of synthesis alpha-lipoic acid, and efficiently solves prior art S- (-)-sulphur
The aggregation problem encountered when sad racemization.
(2) equipment and reagent needed for the present invention are simple, easy to operate, reaction condition is mild, process operation is low in cost, follow
Ring utilizing status is good, high income (yield of 6,8-dichloro-octanoic acid ethyl ester reaches 80% or more), does not generate the pollution such as waste water and dregs
Object meets the technique requirement of industrialized production r-lipoic acid.
(3) present invention not only solves S- (-)-lipoic acid recycling problem, avoids material waste, and substantially
Degree reduces the cost of material of synthesis r-lipoic acid, and new approach is provided for industrial production r-lipoic acid.
Below in conjunction with embodiment, the present invention is described in further detail.
Specific embodiment
Embodiment one:
A kind of processing method that S- (-)-lipoic acid recycles of the present embodiment, its step are as follows:
(1) 20.6g S- (-)-lipoic acid is dissolved in 100mL ethyl acetate, it is 30% that 6.7g concentration, which is then added,
KOH aqueous solution is stirred to react 8h at a temperature of 45 DEG C, obtains S- (-)-lipoic acid reaction solution；
(2) above-mentioned S- (-)-lipoic acid reaction solution is passed through aerator (aeration can be air, low concentration oxygen), exposed
Gas disposal 4h；It is subsequently cooled to 0 DEG C, it is 4 that sulfuric acid to the solution ph that concentration is 5%, which is added dropwise, obtains yellow paste；
(3) above-mentioned yellow paste is dissolved in toluene, 7.8g thionyl chloride is added dropwise, reacts 4h at a temperature of 60 DEG C；
It is subsequently cooled to 10 DEG C, is added dropwise 12mL ethyl alcohol the reaction was continued 3h, obtain 20.0g 6,8-dichloro-octanoic acid ethyl ester.
The yield of the present embodiment 6,8- dicloro caprylate ethyl ester is 83%.
Embodiment two:
A kind of processing method that S- (-)-lipoic acid recycles of the present embodiment, its step are as follows:
(1) 20.6g S- (-)-lipoic acid is dissolved in 100mL toluene, the NaOH water that 8g concentration is 20% is then added
Solution is stirred to react 6h at 50 °C, obtains S- (-)-lipoic acid reaction solution；
(2) above-mentioned S- (-)-lipoic acid reaction solution is passed through aerator (aeration can be air, low concentration oxygen), exposed
Gas disposal 2h；5 DEG C are subsequently cooled to, it is 2 that hydrochloric acid to the solution ph that concentration is 10%, which is added dropwise, obtains yellow paste；
(3) above-mentioned yellow paste is dissolved in toluene, 11.7g thionyl chloride is added dropwise, reacts 3h at a temperature of 60 DEG C；
It is subsequently cooled to 5 DEG C, is added dropwise 20mL ethyl alcohol the reaction was continued 6h, obtain 21.5g 6,8-dichloro-octanoic acid ethyl ester.
The yield of the present embodiment 6,8- dicloro caprylate ethyl ester is 89%.
Claims (10)
1. a kind of processing method that S- (-)-lipoic acid recycles, it is characterised in that the following steps are included:
(1) S- (-)-lipoic acid is dissolved in organic solvent, alkali is then added and carries out basification, obtains S- (-)-lipoic acid
Reaction solution；
(2) S- (-)-lipoic acid reaction solution is subjected to Air Exposure, then carries out acidification and obtains yellow paste；
(3) the yellow paste is dissolved in organic solvent, be added thionyl chloride carry out chlorination after, be added ethyl alcohol after
It is continuous to carry out esterification, obtain 6,8-dichloro-octanoic acid ethyl ester.
2. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: the step
(1) alkali concentration is 20~40% in, according to molar ratio S- (-)-lipoic acid: alkali=1: 1.2~2.0.
3. the processing method that S- (-)-lipoic acid according to claim 1 or 2 recycles, it is characterised in that: the step
Suddenly the temperature of basification is 40~50 DEG C in (1), and the reaction time is 6~9h.
4. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: the step
(2) the Air Exposure time is 2~4h in.
5. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: the step
(2) acid concentration is 5~10% in, carries out acidification at a temperature of 0~5 DEG C, until solution ph is 2~4.
6. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: the step
(3) according to molar ratio S- (-)-lipoic acid in: thionyl chloride=1: 1.0~1.5；The temperature of chlorination is 40~60 DEG C, instead
It is 2~5h between seasonable.
7. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: the step
(3) according to molar ratio S- (-)-lipoic acid in: ethyl alcohol=1: 2.0~3.5；The temperature of esterification is 0~20 DEG C, the reaction time
For 3~6h.
8. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: described organic molten
Agent is toluene, ethyl acetate, t-butyl methyl ether.
9. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: the alkali is hydrogen
Sodium oxide molybdena, potassium hydroxide, calcium hydroxide.
10. the processing method that S- (-)-lipoic acid according to claim 1 recycles, it is characterised in that: the acid is
Hydrochloric acid, sulfuric acid, acetic acid.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113773182A (en) * | 2021-09-10 | 2021-12-10 | 风火轮(上海)生物科技有限公司 | Method for synthesizing 6, 8-dichloro caprylic acid ester |
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Cited By (2)
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