CN110256261A - A kind of chiral separation method being used to prepare left-handed 2- amino-n-butyl alcohol - Google Patents
A kind of chiral separation method being used to prepare left-handed 2- amino-n-butyl alcohol Download PDFInfo
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- CN110256261A CN110256261A CN201910384086.5A CN201910384086A CN110256261A CN 110256261 A CN110256261 A CN 110256261A CN 201910384086 A CN201910384086 A CN 201910384086A CN 110256261 A CN110256261 A CN 110256261A
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- butyl alcohol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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Abstract
The present invention relates to a kind of chiral separation methods for being used to prepare left-handed 2- amino-n-butyl alcohol, and specific steps include: a) with (1S,2S) -1,2- cyclohexanediamine is precursor, prepares target chiral resolving agent through multistep derivative；B) raceme compound 2- amino-n-butyl alcohol is dissolved in ethanol/water mixed solution, and is mixed with the chiral resolving agent of equimolar amounts and copper chloride, there is blue solid precipitation；C) vacuum rotary steam removes the ethyl alcohol in mixed solution, is extracted with ethyl acetate, and filtrate is concentrated, and vacuum drying obtains optically pure levo-compound 2- amino-n-butyl alcohol, ee value is up to 99.0% or more.The beneficial effects of the present invention are: the optical purity of products height that chiral resolving agent synthetic method is simple, reaction condition is mild, isolated, save the cost, suitable industrialization fractionation.
Description
Technical field
The present invention relates to a kind of chiral separation methods for being used to prepare left-handed 2- amino-n-butyl alcohol, belong to a kind of chemical industry neck
The separation method in domain.
Background technique
Mirror surface is symmetrical each other for chirality, i.e. two molecules, is a kind of generally existing feature in nature.For example, constituting
The protein of life entity basic unit is all made of L-type amino acid, and carbohydrate is then all made of D type monosaccharide；Macrocosm
In, the tendril of plant and the screw thread of shell all be unable to do without chirality.It is existing studies have shown that the chiral molecules of various configuration may have
There is completely different physicochemical property.Therefore, just seem particularly important to the high-purity fractionation of raceme compound.Currently, crystallization
Split Method, chromatography, biological resolution method and chemical resolution method etc. are common chiral separation methods.But these methods are all deposited
In some deficiencies, it is difficult to be applied in industrial production.For example, chromatography, which carries out chiral resolution, is unfavorable for industrial applications,
And higher cost.Therefore, exploitation can obtain the difficulty that the high Chiral Separation method of optical purity is present industrial urgent need to resolve
One of topic.
2- amino-n-butyl alcohol is a kind of common medicine intermediate, for example, it can be used for preparing anti-tubercular drug ethamine fourth
Alcohol.Nowadays, single structure that the fractionation generallyd use in industrial production passes through the addition high-purity in 2- amino-n-butyl alcohol raceme
Type mandelic acid (or tartaric acid, glutamic acid), the enantio-selectivity with a kind of configuration is at salt.But there are one for this method
Very important problem: product optics product purity obtained is lower.Therefore, by preparing a kind of novel chiral resolving agent
Realization has great importance to 2- amino-n-butyl alcohol efficient separating.
Summary of the invention
The purpose of the invention is to provide a kind of chiral separation methods for being used to prepare left-handed 2- amino-n-butyl alcohol.It will
After the chiral resolving agent of preparation is mixed with 2- amino-n-butyl alcohol raceme, selectivity occurs under the coordination of copper ion and matches
Position complex-precipitation, to realize to 2- amino-n-butyl alcohol raceme efficient separating.
A kind of chiral separation method being used to prepare left-handed 2- amino-n-butyl alcohol, comprising the following steps:
A, it prepares chiral resolving agent precursor: weighing the left-handed cyclohexanediamine of 114mg and be added in 50mL acetonitrile, stirred under ice bath, to
300mg2- bromine ethyl isocyanate is added dropwise in above-mentioned solution, after reacting 4h, centrifugal filtration washs products therefrom with methylene chloride, very
Sky is dry；
B, it prepares chiral resolving agent: weighing the above-mentioned product of 207mg and be dissolved in 40mL ethyl alcohol, 78mg4,4'- bipyridyl is added, magnetic force stirs
It mixes, and 85oC heating, after reaction 36 hours, vacuum distillation removes solvent, is washed with ethyl acetate, and vacuum drying is to get this
Chiral resolving agent used in patent；
C, split prepare left-handed 2- amino-n-butyl alcohol: weigh 40mg raceme 2- amino-n-butyl alcohol be dissolved in 20mL water/ethyl alcohol mix
It closes in solution, the chiral resolving agent and copper chloride of equimolar amounts is added, there is blue solid precipitation, high speed centrifugation, vacuum rotary steam removes
The ethyl alcohol in mixed solution is removed, is extracted with ethyl acetate, ethyl acetate is extracted and removed water with anhydrous sodium sulfate, is dried in vacuo, is obtained
To optically pure left-handed 2- amino-n-butyl alcohol.
Further, magnetic stirring speed is 150-200r/min, centrifugal rotational speed 8000r/min in step a, and purifying washes
Washing methylene chloride volume used is 30-50mL.
Further, magnetic stirring speed is 150-200r/min in step b, and purifying washs ethyl acetate volume used and is
30-50mL。
Further, centrifugal rotational speed is 8000r/min in the step c, and extracting ethyl acetate volume used is 30-
50mL, anhydrous sodium sulfate quality are 4-8g.
The beneficial effects of the present invention are: chiral resolving agent synthetic method is simple, reaction condition is mild, resolution yield is high, divides
From obtained optical purity of products height, save the cost, it is suitble to industrial production.
Detailed description of the invention
This experiment is further illustrated with reference to the accompanying drawing.
Fig. 1 is the chemical structural drawing of the chiral resolving agent prepared in embodiment one.
Specific embodiment
Presently in connection with specific embodiment, the present invention will be further described, following embodiment be intended to illustrate invention rather than
Limitation of the invention further.
The obtained 2- amino-n-butyl alcohol optical purity of the present invention that splits is identified as follows:
ee=(C S -C R )/(C S -C R )
In formula, ee is indicatedSThe excessive value of type enantiomer, C S And C R It respectively indicatesS- 2- amino-n-butyl alcohol andR- 2- amino -1- fourth
The concentration of alcohol.
Embodiment one:
The preparation of chiral resolving agent includes following two step:
(1) 1.14g (1 is weighedS,2S) -1,2- cyclohexanediamine is added in 150mL acetonitrile, ice bath stirring, is dripped in Xiang Shangshu solution
Add 3.0g2- bromine ethyl isocyanate, there is white solid precipitation, after reacting 4h, centrifugal filtration is washed, very with 100mL methylene chloride
Sky is dry to get the midbody product 3.98g for preparing chiral resolving agent, yield 96%；
(2) it weighs product prepared by 2.07g step 1 and is dissolved in 100mL ethyl alcohol, be added 0.78g4,4'- bipyridyl, magnetic agitation,
And 80oC heating, after reacting 36h, vacuum distillation removes solvent, is washed with 100mL ethyl acetate, is dried in vacuo to get this specially
Chiral resolving agent used in benefit (molecular structure is as shown in Figure 1) 2.65g, yield 93%.
Embodiment two:
300mg raceme compound 2- amino-n-butyl alcohol is weighed to be dissolved in 30mL water/alcohol mixed solution (volume ratio 1:1),
The chiral resolving agent (1.92g) and copper chloride (0.455g) of equimolar amounts is added, there is blue solid precipitation, is centrifuged, after fractionation
Solution revolving removes ethyl alcohol therein, is extracted with 60mL ethyl acetate, and the drying of 15g anhydrous sodium sulfate is added in organic extractant phase liquid,
Vacuum distillation, obtains left-handed 2- amino-n-butyl alcohol 148mg of high-purity, measures ee value greater than 99%.
Embodiment three:
10g raceme compound 2- amino-n-butyl alcohol is weighed to be dissolved in 800mL water/alcohol mixed solution (volume ratio 1:1),
The chiral resolving agent (64g) and copper chloride (15.1g) of equimolar amounts is added, there is blue solid precipitation, is centrifuged, by solution after fractionation
Vacuum rotary steam removes ethyl alcohol therein, is extracted with 300mL ethyl acetate, and the drying of 35g anhydrous sodium sulfate is added in organic extractant phase liquid,
Vacuum distillation, obtains left-handed 2- amino-n-butyl alcohol 4.92g of high-purity, measures ee value greater than 99%.
Claims (4)
1. a kind of chiral separation method for being used to prepare left-handed 2- amino-n-butyl alcohol, steps are as follows:
A, it prepares chiral resolving agent precursor: weighing the left-handed cyclohexanediamine of 114mg and be added in 50mL acetonitrile, stirred under ice bath, to
300mg2- bromine ethyl isocyanate is added dropwise in above-mentioned solution, after reacting 4h, centrifugal filtration washs products therefrom with methylene chloride, very
Sky is dry；
B, it prepares chiral resolving agent: weighing the above-mentioned product of 207mg and be dissolved in 40mL ethyl alcohol, 78mg4,4'- bipyridyl is added, magnetic force stirs
It mixes, and 85oC heating, after reaction 36 hours, vacuum distillation removes solvent, is washed with ethyl acetate, and vacuum drying is to get this
Chiral resolving agent used in patent；
C, split prepare left-handed 2- amino-n-butyl alcohol: weigh 40mg raceme 2- amino-n-butyl alcohol be dissolved in 20mL water/ethyl alcohol mix
It closes in solution, the chiral resolving agent and copper chloride of equimolar amounts is added, there is blue solid precipitation, high speed centrifugation, vacuum rotary steam removes
The ethyl alcohol in mixed solution is removed, ethyl acetate is extracted and removed water with anhydrous sodium sulfate, and vacuum rotary steam removes ethyl acetate, and vacuum is dry
It is dry, obtain optically pure left-handed 2- amino-n-butyl alcohol.
2. a kind of chiral separation method for being used to prepare left-handed 2- amino-n-butyl alcohol according to claim 1, it is characterized in that:
Magnetic stirring speed is 150-200r/min, centrifugal rotational speed 8000r/min in the step a, and dichloromethane used is washed in purifying
Alkane volume is 30-50mL.
3. a kind of chiral separation method for being used to prepare left-handed 2- amino-n-butyl alcohol according to claim 1, it is characterized in that:
Magnetic stirring speed is 150-200r/min in the step b, and it is 30-50mL that ethyl acetate volume used is washed in purifying.
4. a kind of chiral separation method for being used to prepare left-handed 2- amino-n-butyl alcohol according to claim 1, it is characterized in that:
Centrifugal rotational speed is 8000r/min in the step c, and extracting ethyl acetate volume used is 30-50mL, and anhydrous sodium sulfate quality is
4-8g。
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| CN2019101274942 | 2019-02-20 | ||
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114409491A (en) * | 2020-10-28 | 2022-04-29 | 中国科学院大连化学物理研究所 | Method for preparing trans-D-dichlorochrysanthemic acid by resolution of trans-dichlorochrysanthemic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006036729A (en) * | 2004-07-30 | 2006-02-09 | Nippon Soda Co Ltd | Method for producing optically active alcohol derivative |
| CN101489983A (en) * | 2006-07-11 | 2009-07-22 | 克里斯托夫·马克 | Method for producing optically active amines |
| CN101863779A (en) * | 2010-05-11 | 2010-10-20 | 东北农业大学 | Method for preparing chiral compound S-(+)- and R-(-)-2-amino butanol |
| CN106905100A (en) * | 2017-04-06 | 2017-06-30 | 联化科技（台州）有限公司 | The method for splitting and its intermediate of chiral aminated compounds |
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- 2019-05-09 CN CN201910384086.5A patent/CN110256261B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006036729A (en) * | 2004-07-30 | 2006-02-09 | Nippon Soda Co Ltd | Method for producing optically active alcohol derivative |
| CN101489983A (en) * | 2006-07-11 | 2009-07-22 | 克里斯托夫·马克 | Method for producing optically active amines |
| CN101863779A (en) * | 2010-05-11 | 2010-10-20 | 东北农业大学 | Method for preparing chiral compound S-(+)- and R-(-)-2-amino butanol |
| CN106905100A (en) * | 2017-04-06 | 2017-06-30 | 联化科技（台州）有限公司 | The method for splitting and its intermediate of chiral aminated compounds |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114409491A (en) * | 2020-10-28 | 2022-04-29 | 中国科学院大连化学物理研究所 | Method for preparing trans-D-dichlorochrysanthemic acid by resolution of trans-dichlorochrysanthemic acid |
| CN114409491B (en) * | 2020-10-28 | 2023-02-21 | 中国科学院大连化学物理研究所 | Method for preparing trans-D-dichlorochrysanthemic acid by resolution of trans-dichlorochrysanthemic acid |
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