CN106397239B - Amino-acid ester cationic chiral ionic liquid and preparation method thereof - Google Patents
Amino-acid ester cationic chiral ionic liquid and preparation method thereof Download PDFInfo
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- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0277—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature
- B01J31/0278—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre
- B01J31/0279—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the cationic portion being acyclic or nitrogen being a substituent on a ring
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- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
- C07C319/12—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols by reactions not involving the formation of mercapto groups
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
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Abstract
A kind of amino-acid ester cationic chiral ionic liquid of present invention offer and preparation method thereof.The amino-acid ester cationic chiral ionic liquid structural formula is as follows.Wherein, R is the variable groups of alpha amino acid；R ' is the alkyl that carbon atom number is 1~3；X‑For BF4 ‑、PF6 ‑、HSO4 ‑In one kind.The chiral position of the amino-acid ester cationic chiral ionic liquid of the present invention is connected with bulky group on amino acid cation on amino, stereoselectivity is stronger, has structure diversity and designability.
Description
Technical field
The present invention relates to ionic liquid preparation field more particularly to a kind of amino-acid ester cationic chiral ionic liquid and
Preparation method.
Background technology
Ionic liquid be made of organic cation and organic anion or inorganic anion, in room temperature or close to room temperature
At a temperature of be in liquid condition salt.Ionic liquid has excellent physicochemical properties, such as there is steam to force down, volatility
Small, good conductivity, polarity are strong, electrochemical window mouth width, thermal stability are high, and have to a large amount of inorganic and organic substances preferable
Dissolubility and catalytic performance, and ionic liquid has can modify/zwitterion the structure of modulation, and can also recycle, because
This is considered as substituting the novel green solvent for commonly using volatile organic solvent, is widely applied in chemical field.
As ionic liquid designs the continuous development of synthetic technology, some scholars begin one's study in ionic liquid in recent years
Design introduces chiral centre, to expand the research field and application range of ionic liquid.Chiral ionic liquid combines ionic liquid
The advantages of body and chiral material and characteristic, can be applied to chiral Recognition, asymmetric syntheses, Chiral Separation, stereoselective polymerization,
The fields such as gas-chromatography, NMR shift reagens and liquid crystal.Therefore, development chiral ionic liquid has important in chiral synthesis field
Realistic meaning.
Currently, having many reports in terms of the synthesis of chiral ionic liquid and its application study, such as with australene, peppermint
Alcohol, ephedrine etc. have synthesized a series of chiral ionic liquids as chiral source.Amino acid is a kind of natural chiral source, by amino
Acid is easy to get as chiral source synthesis of chiral ionic liquid starting material, greatly reduces the cost of synthesis of chiral ionic liquid.In recent years,
The report for synthesizing ionic liquid using amino acid as chiral source gradually increases, the Chinese patent text as disclosed in 11 days December in 2002
It offers and discloses a kind of l-amino acid sulfate type chiral ionic liquid and preparation method thereof, on December 11st, 2002 in CN1383920A
A kind of l-amino acid hydrogen sulfate salt form chiral ionic liquid and its system are disclosed in disclosed Chinese patent literature CN1383921A
Another l-amino acid sulfuric acid is disclosed in Chinese patent literature CN104693054A disclosed in Preparation Method, 10 days June in 2015
It is disclosed in Chinese patent literature CN1621152A disclosed in salt form chiral ionic liquid and preparation method thereof, 1 day June in 2005
A kind of ionic liquid and preparation method of amino-acid ester cation.These disclosed patent documents enrich amino acid chiral ion
The type of liquid is provided and is benefited our pursuits for the application of ionic liquid.But the amino acid chiral ion of above patent document description
The preparation method of liquid is coarse, and amino acid cationic structural is simple (there are carboxyl, amino in structure), and this strongly limits it to make
Use range.
Invention content
The problem of in view of background technology, the purpose of the present invention is to provide a kind of amino-acid ester cationic chiralitys
Ionic liquid and preparation method thereof, the chiral position of the amino-acid ester cationic chiral ionic liquid is in amino acid cation
On, bulky group is connected on amino, stereoselectivity is stronger, has structure diversity and designability.
In order to achieve the above object, in one aspect of the invention, the present invention provides a kind of amino-acid ester cationic hands
Property ionic liquid, structural formula are as follows.Wherein, R is the variable groups of a-amino acid；R ' is the alkyl that carbon atom number is 1~3；
X-For BF4 -、PF6 -、HSO4 -In one kind.
In another aspect of this invention, the present invention provides a kind of preparations of amino-acid ester cationic chiral ionic liquid
Method is used to prepare the amino-acid ester cationic chiral ionic liquid described in one aspect of the present invention, including step：(1) -5
It DEG C is reacted hereinafter, thionyl chloride is added drop-wise in anhydrous R '-OH, is warming up to later after room temperature and a-amino acid is added, and
It is reacted at 50 DEG C~80 DEG C, removes impurity later, obtain amino acid ester hydrochlorides；(2) amino acid ester hydrochlorides are dissolved
In deionized water, pH=5~6 are adjusted with lye, after through separating-purifying obtain amino-acid ester；(3) amino-acid ester is placed in
In three-neck flask, it is passed through nitrogen protection, is warming up to 50 DEG C~60 DEG C, the mixed liquor that alcohols solvent and benzaldehyde is added carries out instead
It answers, removes impurity after reaction, obtain amino-acid ester schiff bases；(4) amino-acid ester schiff bases are dissolved in alcohols solvent,
0 DEG C or less addition sodium borohydride, is warming up to room temperature after adding and is reacted, and later plus deionized water is quenched, and is adjusted with acid solution
PH=6~7 obtain amino-acid ester secondary amine intermediate after separating-purifying；(5) alcohols is added into amino-acid ester secondary amine intermediate
The mixed solution of solvent and bromination of n-butane is warming up to 50 DEG C~65 DEG C and is reacted, removes impurity after reaction, obtain ammonia
Base acid esters Bromide；(6) after mixing amino-acid ester Bromide with Me-X, deionized water is added or acetone is reacted, Me choosings
From Na or K, impurity is removed after reaction to get to amino-acid ester cationic chiral ionic liquid.
Compared with the existing technology, beneficial effects of the present invention are：
(1) the chiral position of amino-acid ester cationic chiral ionic liquid of the invention is on amino acid cation, amino
On be connected with bulky group, stereoselectivity is stronger, have structure diversity and designability.
(2) amino-acid ester cationic chiral ionic liquid of the invention both has the non-volatile, nontoxic of ionic liquid, nothing
Pollution, the characteristics such as liquid range is wide, steam forces down, good conductivity, polarity are strong, but it is highly selective, chiral with chiral material
The characteristics such as inductive effect, can be used for chiral catalysis and chiral separation, be very suitable for Fine Chemical large-scale production.
(3) in the preparation method of amino-acid ester cationic chiral ionic liquid of the present invention, raw material sources are abundant, price is low
It is honest and clean, easy to operate.
Specific implementation mode
The following detailed description of amino-acid ester cationic chiral ionic liquid according to the present invention and preparation method thereof.
Illustrate amino-acid ester cationic chiral ionic liquid according to a first aspect of the present invention first.
The structural formula of amino-acid ester cationic chiral ionic liquid according to a first aspect of the present invention is as follows：
Wherein, R is the variable groups of a-amino acid；R ' is the alkyl that carbon atom number is 1~3；X-For BF4 -、PF6 -、HSO4 -
In one kind.
In the amino-acid ester cationic chiral ionic liquid described according to a first aspect of the present invention, amino-acid ester sun from
The chiral position of subtype chiral ionic liquid is connected with large volume phenyl ring on amino acid cation, on amino, and stereoselectivity is more
By force, there is structure diversity and designability.
In the amino-acid ester cationic chiral ionic liquid described according to a first aspect of the present invention, it is preferable that R ' is-
CH3Or-CH2CH3。
In the amino-acid ester cationic chiral ionic liquid described according to a first aspect of the present invention, a-amino acid D-
In cysteine, L-cysteine, D-Ser, Serine, D-alanine, l-Alanine, D-Val, Valine
It is a kind of.
Secondly the preparation method of the amino-acid ester cationic chiral ionic liquid of explanation according to a second aspect of the present invention.
The preparation method of amino-acid ester cationic chiral ionic liquid according to a second aspect of the present invention is used to prepare this
Amino-acid ester cationic chiral ionic liquid described in invention first aspect, including step：(1) at -5 DEG C hereinafter, by chlorination
Sulfoxide, which is added drop-wise in anhydrous R '-OH, to be reacted, and is warming up to later after room temperature and a-amino acid is added, and at 50 DEG C~80 DEG C into
Row reaction, removes impurity, obtains amino acid ester hydrochlorides later；(2) in deionized water by amino acid ester hydrochlorides dissolving, it uses
Lye adjusts pH=5~6, after through separating-purifying obtain amino-acid ester；(3) amino-acid ester is placed in three-neck flask, is passed through
Nitrogen protection is warming up to 50 DEG C~60 DEG C, and the mixed liquor that alcohols solvent and benzaldehyde is added is reacted, and is removed after reaction
Impurity obtains amino-acid ester schiff bases；(4) amino-acid ester schiff bases are dissolved in alcohols solvent, hydroboration is added at 0 DEG C or less
Sodium is warming up to room temperature after adding and is reacted, and later plus deionized water is quenched, and adjusts pH=6~7 with acid solution, is carried through separation
Amino-acid ester secondary amine intermediate is obtained after pure；(5) alcohols solvent and bromination of n-butane are added into amino-acid ester secondary amine intermediate
Mixed solution, be warming up to 50 DEG C~65 DEG C and reacted, remove impurity after reaction, obtain amino-acid ester Bromide；(6)
After amino-acid ester Bromide is mixed with Me-X, deionized water is added or acetone is reacted, Me is selected from Na or K, and reaction terminates
Impurity is removed afterwards to get to amino-acid ester cationic chiral ionic liquid.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (1), need to control rate of addition when meeting alcohol R '-OH due to thionyl chloride and release a large amount of heat, therefore thionyl chloride is added dropwise
Reaction temperature is set to maintain -5 DEG C or less always.Preferably, maintain temperature that thionyl chloride is added drop-wise to nothing at -15 DEG C~-10 DEG C
It is reacted in water R '-OH.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (1), the reaction time of thionyl chloride and anhydrous R '-OH can be 1h~2h.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (1), a-amino acid, thionyl chloride, R '-OH the ratio between the amount of substance be 1:(1.1~1.5):(12~35).
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (1), the time reacted at 50 DEG C~80 DEG C can be 3h~4h.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (1), when removing impurity, vacuum distillation can be first passed through and remove low-boiling point material.Vacuum distillation can be common vacuum distillation
Or revolving.Vacuum distillation can also further be purified after removing low-boiling point material by recrystallization or column chromatography.Weight
The solvent used when crystallization can be absolute ethyl alcohol or absolute methanol.Dichloromethane and absolute methanol or anhydrous can be used when column chromatography
Ethyl alcohol.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (2), lye is NaOH or KOH solution.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (2), the concentration of lye can be 1mol/L~2mol/L.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (2), the step of separating-purifying, may include：Extraction, drier water removal, filters removing drier, removes extraction liquid separation
Agent.Wherein, extractant can be dichloromethane.Drier can be anhydrous sodium sulfate or anhydrous magnesium sulfate.It can lead to when removing extractant
Cross vacuum distillation.Vacuum distillation can be common vacuum distillation or revolving.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (3), the ratio between amount of substance of amino-acid ester and benzaldehyde is 1:(1~1.5).
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (3), alcohols solvent can be absolute ethyl alcohol or absolute methanol.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (3), the reaction time is 3h~8h at 50 DEG C~60 DEG C.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (3), when removing impurity, vacuum distillation can be first passed through and remove low-boiling point material.Vacuum distillation can be common vacuum distillation
Or revolving.Vacuum distillation can also further be purified after removing low-boiling point material by recrystallization or column chromatography.Weight
The solvent used when crystallization can be absolute ethyl alcohol or absolute methanol.Dichloromethane and absolute methanol or anhydrous can be used when column chromatography
Ethyl alcohol.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (4), the ratio between sodium borohydride and the amount of substance of amino-acid ester schiff bases are (1.5~4.5):1.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (4), alcohols solvent can be absolute ethyl alcohol or absolute methanol.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (4), sodium borohydride is added portionwise at 0 DEG C or less, room temperature reaction 1h~2h is warming up to after adding.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (4), acid solution can be hydrochloric acid solution.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (4), the step of separating-purifying, may include：Extraction, drier water removal, filters removing drier, removes extractant liquid separation
And the alcohols solvent being added.Wherein, extractant can be dichloromethane.Drier can be anhydrous sodium sulfate or anhydrous magnesium sulfate.
It can pass through vacuum distillation when removing extractant and alcohols solvent.Vacuum distillation can be common vacuum distillation or revolving.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (5), the ratio between bromination of n-butane and the amount of substance of amino-acid ester secondary amine intermediate are (2~2.5):1.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (5), 5h~8h is reacted at 50 DEG C~65 DEG C.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (5), when removing impurity, vacuum distillation can be first passed through and remove low-boiling point material.Vacuum distillation can be common vacuum distillation
Or revolving.Vacuum distillation can also further be purified after removing low-boiling point material by recrystallization or column chromatography.Weight
The solvent used when crystallization can be absolute ethyl alcohol or absolute methanol.Dichloromethane and absolute methanol or anhydrous can be used when column chromatography
Ethyl alcohol.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (6), the ratio between amount of substance of amino-acid ester Bromide and Me-X is 1:(1~1.5).
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (6), Me-X can be NaBF4、KBF4、KPF6、NaPF6、NaHSO4、KHSO4。
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (6), the reaction time can be to stir 3h~for 24 hours at room temperature.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (6), when making solvent with deionized water, stratification, discards supernatant liquid after reaction, by lower liquid second
After ether washing, vacuum drying is to get to amino-acid ester cationic chiral ionic liquid.
In the preparation method of the amino-acid ester cationic chiral ionic liquid described according to a second aspect of the present invention,
In step (6), when with acetone as solvent, after reaction, filters removing solid MeBr (NaBr or KBr) and unreacted is complete
Raw material, then remove acetone to get to amino-acid ester cationic chiral ionic liquid.Removing acetone can be steamed by depressurizing
It evaporates.Vacuum distillation can be common vacuum distillation or revolving.
With reference to embodiment, the application is expanded on further.It should be understood that these embodiments be merely to illustrate the application without
For limiting scope of the present application.
Embodiment 1
(1) 60mL (1.48mol) absolute methanol is taken to be added in three-neck flasks of the 250mL with drying tube, in low temperature perseverance
- 13 DEG C are cooled in tepidarium hereinafter, 4.0mL (0.055mol) SOCl is slowly added dropwise under magnetic agitation2, control reaction when dropwise addition
Temperature is at -10 DEG C or less.It after being added dropwise, is warmed to room temperature naturally, continues to stir 2h.Backward three-neck flask in be added
4.19g (0.047mol) l-Alanine is warming up to 80 DEG C, is stirred to react 4h after reacting at room temperature 2h.Period is monitored with TLC reacts
After reaching balance, stops reaction, product is rotated, after steaming solvent, a large amount of faint yellow acicular crystals, as L- third occurs
Propylhomoserin methyl ester hydrochloride is put into 60 DEG C of drying 6h of vacuum drying chamber, yield 82.5%.
(2) it weighs 4.33g (0.031mol) l-Alanine methyl ester hydrochloride to be dissolved in 15mL deionized waters, uses 2mol/L
NaOH solution adjust pH=6.With the extraction of the dichloromethane of 60mL three times, liquid separation, with anhydrous sodium sulfate drying water removal, filter and remove
Anhydrous sodium sulfate, finally revolving removing dichloromethane are removed, 3.09g (0.030mol) l-Alanine methyl esters is obtained.
(3) 2.89g (0.028mol) l-Alanine methyl esters is dissolved in 30mL absolute methanols, is added to tri- necks of 100mL burning
In bottle, it is passed through nitrogen protection, will be slowly added dropwise to above-mentioned dissolved with the 10mL absolute methanol solutions of 3.1mL (0.036mol) benzaldehyde
It in mixed liquor, waits being added dropwise, temperature is risen to 60 DEG C, constant temperature stirs 3h.TLC is detected to benzaldehyde to react completely.Reaction knot
Shu Hou, decompression steam solvent, yellow solid, as l-Alanine methyl esters schiff bases are obtained, with absolute methanol and dichloromethane column
Chromatographic purification, yield 76.10%.
(4) 3.28g (0.017mol) l-Alanine methyl esters schiff bases are dissolved in 30mL absolute methanols, low temperature is stirred to react
It is cooled to 0 DEG C in bath hereinafter, 2.15g (0.057mol) sodium borohydride is added portionwise, adds rear clear-cutting forestland to reacting at room temperature 2h,
With TLC monitoring reactions after, pH=7 is adjusted with 10% hydrochloric acid, with the extraction of the dichloromethane of 60mL three times, liquid separation plus
Anhydrous magnesium sulfate drying water removal filters removing anhydrous magnesium sulfate, removes solvent under reduced pressure, obtains brown liquid, as l-Alanine
Methyl esters secondary amine intermediate, yield 66.4%.
(5) it takes 0.8395g (0.0041mol) l-Alanine methyl esters secondary amine intermediate to be dissolved in 30mL absolute methanols, is added
1.27g (0.0093mol) bromination of n-butane, magnetic agitation are heated to 65 DEG C and react 8h, and TLC is monitored to the reaction was complete, and decompression is steamed
Go out solvent, dark brown viscous shape liquid l-Alanine methyl esters Bromide is obtained, with absolute methanol and dichloromethane column chromatography for separation
Obtain sterling, yield 69.9%.
(6) it takes 0.45g (0.00118mol) l-Alanine methyl esters Bromide in 50mL there-necked flasks, 0.21g is added
(0.00118mol)KPF6, 10mL deionized waters are added, reaction 10h is stirred at room temperature, stops reaction, stratification discards
Layer liquid, after lower liquid wash twice with 10mL ether, be dried in vacuo to get to l-Alanine methyl esters cationic chirality from
Sub- liquid, yield 86%.
Embodiment 2
(1) 120mL (2.96mol) absolute methanol is taken to be added in three-neck flasks of the 250mL with drying tube, in low temperature perseverance
- 15 DEG C are allowed to cool in tepidarium hereinafter, 10mL (0.138mol) SOCl is slowly added dropwise under magnetic agitation2, when dropwise addition controls
Reaction temperature is at -10 DEG C or less.The reaction was continued after being added dropwise 1h.Naturally it is warmed to room temperature, 14.74g (0.126mol) is added
D-Val stops reaction after being heated to 60 DEG C of reaction 4h under magnetic stirring.After product at reduced pressure is steamed solvent, obtain
D-Val methyl ester hydrochloride is yellow, viscous liquid, yield 93%.
(2) dissolving of 11.15g (0.085mol) D-Val methyl ester hydrochloride is taken in deionized water, with 2mol/L's
NaOH solution adjusts pH=6.With the extraction of the dichloromethane of 60mL three times, liquid separation, with anhydrous sodium sulfate drying water removal, filter and remove
Anhydrous sodium sulfate, revolving remove dichloromethane, obtain 10.62g (0.081mol) D-Val methyl esters.
(3) it takes 8.66g (0.074mol) D-Val methyl esters to be placed in 250mL three-neck flasks, 80mL absolute methanols is added
It makes it dissolve, adds 9.12g (0.086mol) benzaldehyde, be passed through nitrogen protection, be warming up to 60 DEG C later, continue to be stirred to react
8h.After completion of the reaction, removed under reduced pressure major part solvent, cooling place precipitate crystal, and D-Val methyl esters is obtained after filtering, drying
Schiff bases are recrystallized using absolute methanol and are purified, obtain sterling D-Val methyl esters schiff bases, yield 83%.
(4) 4.12g (0.019mol) D-Val methyl esters schiff bases are taken to be dissolved in 30mL absolute methanols, low temperature is stirred to react
It is cooled to 0 DEG C in bath hereinafter, 2.01g (0.0532mol) sodium borohydride is added portionwise, adds rear clear-cutting forestland to reacting at room temperature
2h, with TLC monitoring reactions after, with 10% hydrochloric acid tune pH=7, with the dichloromethane extraction of 60mL three times, liquid separation plus
Anhydrous magnesium sulfate drying water removal, suction filtration remove anhydrous magnesium sulfate, decompression steams solvent, obtain weak yellow liquid, i.e. D-Val
Methyl esters secondary amine intermediate, yield 63.2%.
(5) it takes 0.91g (0.0041mol) D-Val methyl esters secondary amine intermediate to be dissolved in 30mL absolute methanols, is added
1.27g (0.0093mol) bromination of n-butane, magnetic agitation are heated to 65 DEG C and react 8h, and TLC is monitored to the reaction was complete, and decompression is steamed
Go out solvent, obtain yellow, viscous liquid, as D-Val methyl esters Bromide, with absolute methanol and dichloromethane column chromatography point
Sterling, yield 80.3% are obtained from after.
(6) it takes 0.53g (0.00125mol) D-Val methyl esters Bromide in 50mL there-necked flasks, 0.23g is added
(0.00125mol)KPF6, 10mL acetone is added, stirring at normal temperature 10h stops reaction, filters and removes solid KBr, then rotates
Acetone is removed to get to D-Val methyl esters cationic chiral ionic liquid, yield 82%.
Claims (9)
1. a kind of preparation method of amino-acid ester cationic chiral ionic liquid, which is characterized in that including step：
(1) it is reacted at -5 DEG C hereinafter, thionyl chloride is added drop-wise in anhydrous R '-OH, α-is added after being warming up to room temperature later
Amino acid, and reacted at 50 DEG C~80 DEG C, impurity is removed later, obtains amino acid ester hydrochlorides；
(2) by amino acid ester hydrochlorides dissolving in deionized water, with lye adjust pH=5~6, after obtained through separating-purifying
Amino-acid ester；
(3) amino-acid ester is placed in three-neck flask, is passed through nitrogen protection, be warming up to 50 DEG C~60 DEG C, be added alcohols solvent and
The mixed liquor of benzaldehyde is reacted, and removes impurity after reaction, obtains amino-acid ester schiff bases；
(4) amino-acid ester schiff bases are dissolved in alcohols solvent, sodium borohydride is added at 0 DEG C or less, room temperature is warming up to after adding
It is reacted, later plus deionized water is quenched, and adjusts pH=6~7 with acid solution, amino-acid ester secondary amine is obtained after separating-purifying
Intermediate；
(5) into amino-acid ester secondary amine intermediate be added alcohols solvent and bromination of n-butane mixed solution, be warming up to 50 DEG C~
65 DEG C are reacted, and remove impurity after reaction, obtain amino-acid ester Bromide；
(6) after mixing amino-acid ester Bromide with Me-X, deionized water is added or acetone is reacted, Me is selected from Na or K, instead
Impurity is removed after answering to get to amino-acid ester cationic chiral ionic liquid；
The structural formula of the amino-acid ester cationic chiral ionic liquid is as follows：
Wherein, R is the variable groups of a-amino acid；R ' is the alkyl that carbon atom number is 1~3；X-For BF4 -、PF6 -、HSO4 -In
It is a kind of.
2. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that R '
For-CH3Or-CH2CH3。
3. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that α-ammonia
Base acid is D-Cys, L-cysteine, D-Ser, Serine, D-alanine, l-Alanine, D-Val, L- figured silk fabrics
One kind in propylhomoserin.
4. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that
In step (1), cryogenic temperature is -15 DEG C~-10 DEG C.
5. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that
In step (1), a-amino acid, thionyl chloride, R '-OH the ratio between the amount of substance be 1:(1.1~1.5):(12~35).
6. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that
In step (3), the ratio between amount of substance of amino-acid ester and benzaldehyde is 1:(1~1.5).
7. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that
In step (4), the ratio between sodium borohydride and the amount of substance of amino-acid ester schiff bases are (1.5~4.5):1.
8. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that
In step (5), the ratio between bromination of n-butane and the amount of substance of amino-acid ester secondary amine intermediate are (2~2.5):1.
9. the preparation method of amino-acid ester cationic chiral ionic liquid according to claim 1, which is characterized in that
In step (6), the ratio between amount of substance of amino-acid ester Bromide and Me-X is 1:(1~1.5).
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1621152A (en) * | 2004-10-11 | 2005-06-01 | 北京大学 | Ion liquid of amino acid ester cation and its preparation method |
| CN104693054A (en) * | 2013-12-04 | 2015-06-10 | 青岛惠城石化科技有限公司 | L-amino acid sulfate type chiral ionic liquid and preparation method thereof |
| CN105152949A (en) * | 2015-08-18 | 2015-12-16 | 唐山师范学院 | Amino-acid ester derivative cation type chiral ionic liquid and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1621152A (en) * | 2004-10-11 | 2005-06-01 | 北京大学 | Ion liquid of amino acid ester cation and its preparation method |
| CN104693054A (en) * | 2013-12-04 | 2015-06-10 | 青岛惠城石化科技有限公司 | L-amino acid sulfate type chiral ionic liquid and preparation method thereof |
| CN105152949A (en) * | 2015-08-18 | 2015-12-16 | 唐山师范学院 | Amino-acid ester derivative cation type chiral ionic liquid and preparation method thereof |
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