CN100462346C - Preparation method for isodeca-deca-isoprene-yl alcohol - Google Patents
Preparation method for isodeca-deca-isoprene-yl alcohol Download PDFInfo
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- CN100462346C CN100462346C CNB2005100109255A CN200510010925A CN100462346C CN 100462346 C CN100462346 C CN 100462346C CN B2005100109255 A CNB2005100109255 A CN B2005100109255A CN 200510010925 A CN200510010925 A CN 200510010925A CN 100462346 C CN100462346 C CN 100462346C
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Abstract
The present invention is preparation process of isodecyl deca-isoprene alcohol. The present invention adopts solanesol as initial material to prepare derivative isodecyl deca-isoprene alcohol with 10 double bonds and 50 carbon atoms through five chemical reaction steps, including halogenation, condensation, forming ketone, addition and hydration inside the identical unit. The process has product purity over 90 %, total yield of 83-85 % and mild reaction condition, and may be used in industrial production.
Description
Technical field
The present invention relates to field of medicine preparing technology.Be specifically related to a kind of preparation method for isodeca-deca-isoprene-yl alcohol.
Background technology
About the existing report of the preparation method of isodecyl alcohol deca-isopentyl alcohol, main preparation method has as follows:
(1) Rueggt etc., J Helv chim Acta, 1959,42:2616-2621
(2)Naruta，J?org?chem.1980，45(21)：4091—4104。
(3)Daniel?Dacvid?West，US?2002/0156302?A1
But there is more defective in above-mentioned preparation method, and for example the costing an arm and a leg of reagent, severe reaction conditions, synthetic route are loaded down with trivial details ... or the like.
Summary of the invention
Technical problem to be solved by this invention is to overcome above-mentioned weak point, designs a kind of preparation method of easy and simple to handle, lower-cost isodecyl alcohol deca-isopentyl alcohol.
The invention provides a kind of preparation method of isodecyl alcohol deca-isopentyl alcohol, this method comprises the following steps:
(1) halogenating reaction prepares compound (III)
In reaction vessel, put into dimethyl formamide-petroleum ether solvent, under-20 ℃～10 ℃ conditions, in reactor, drip PX
3, when stirring, add the eggplant Buddhist nun alcohol (II) that is dissolved in advance in dimethyl formamide-petroleum ether solvent, continue to stir 1～5h and carry out halogenating reaction, reaction is finished, and uses petroleum ether extraction, and water washing discards water layer, the oil reservoir anhydrous Na
2SO
4Drying removes by filter siccative, obtains solid chemical compound (III) after removing the liquid cooling behind the solvent;
(2) preparation compound (IV):
In reaction vessel, add the sodium alkoxide alcoholic solution, add acetylacetic ester again, be warming up to 30 ℃ and stir 1.5h, the petroleum ether solution of the compound (III) that dropping step (1) makes is warming up to 60 ℃ then and stirs 1～5h, carries out substituted condensed reaction, reaction is complete to make compound (IV), need not handle directly entering the next step;
(3) preparation compound (V):
The reaction solution that contains compound (IV) that step (2) is made is heated to backflow, adds alkaline solution, continues stirring and refluxing 1～5h, and reaction is finished, and uses ethyl acetate extraction, after water washing, adds anhydrous Na
2SO
4Drying, the elimination siccative, remove behind the solvent compound (V);
(4) preparation isodecyl alcohol deca-isopentyl alcohol (I):
Add the tetrahydrofuran solution of vinyl halogenation magnesium in reaction vessel, and then add the tetrahydrofuran solution that contains compound (V), stirring reaction 2～8h makes compound (VI) after reacting completely, and adds saturated NH in reactant
4The Cl aqueous solution, stirring at room 1-3h reaction that is hydrolyzed, reaction is finished, and uses ethyl acetate extraction, after water washing, adds anhydrous MgSO
4Drying, the elimination siccative obtains isodecyl alcohol deca-isopentyl alcohol (I) crude product behind the desolventizing, again through chromatography, the sherwood oil wash-out with 2% ethyl acetate, obtain colourless oil liquid, behind crystallization purifying content 90% pure product (I).
Synthetic route of the present invention is formula as follows:
Wherein: PX
3In X=Cl or I;
CH
3COCH
2R ' among the COOR '=CH
3Or C
2H
5
R=CH among the RONa
3Or C
2H
5
H
2X=Cl among C=CH-MgX or I.
The objective of the invention is to solve that existing synthetic route is loaded down with trivial details, severe reaction conditions, the expensive deficiency of reagent, provide a kind of efficient, easy, inexpensive and be applicable to the preparation method of the isodecyl alcohol deca-isopentyl alcohol of suitability for industrialized production.
The present invention is a starting raw material with eggplant Buddhist nun alcohol (II), elder generation and PX
3(-X for-Cl or-I) carry out halogenating reaction at low temperatures, obtain the compound (III) of halogen atom functional group through processes such as extraction, washing, drying, filtration, precipitations.Carry out substituted condensed reaction with sodium alkoxide and acetylacetic ester under refluxing again, reaction finishes, and directly uses alkali, and solution hydrolysis under refluxing obtains eggplant Thessaloniki ketone (V) through extraction, washing, drying, filtration, precipitation, not purified Yu Geshi agent-halogen vinyl magnesium CH
2(X=Cl I) carries out addition reaction to=CH-Mg-X, generates (VI) not treated available saturated NH
4The Cl aqueous solution is hydrolyzed, obtain containing the thick isodecyl alcohol deca-isopentyl alcohol (I) of 10 two keys, 50 carbon atoms through processing such as extraction, drying, filtration, precipitations, can obtain content through chromatography, crystallization〉90% product, a mole total recovery is 83～85%.
Synthetic route is as follows:
Wherein: PX
3In X=Cl or I;
CH
3COCH
2R ' among the COOR '=CH
3Or C
2H
5
R=CH among the RONa
3Or C
2H
5
H
2X=Cl among C=CH-MgX or I.
In halogenating reaction of the present invention, raw material eggplant Buddhist nun alcohol (II) content 〉=90% with sherwood oil and dimethyl formamide dissolving, adds PX
3, eggplant Buddhist nun alcohol (II) and PX
3The mol ratio of (X=I, Cl) is 1:1.0～2.5, and the consumption of solvent is not crucial especially ,-20 °～10 ℃ reaction 1～5h.Use petroleum ether extraction, dry, filter, precipitation gets compound (III), purifying and sodium alkoxide do not react with the condenses that acetylacetic ester carries out condensation, its ratio of components is: compound (III): acetylacetic ester: the mol ratio of sodium alkoxide (sodium methylate or sodium ethylate) is 1:3:2.8, wherein ester can be methyl esters, ethyl ester all can, solvent is corresponding pure and mild sherwood oil, be reflected at 30 ℃ and stir 1.5h, sodium alkoxide carries out substitution reaction with acetylacetic ester earlier, adds compound (III) then, under agitation is warming up to 60 ℃ of reaction 1～5h, carry out substituted condensed reaction, reaction is finished and to be made compound (IV), and reaction mixture adds alkaline solution (NaOH or the KOH) hydrolysis 1～5h down that refluxes, compound (III) (W): alkali (W)=1: 2～5, reaction is finished, use ethyl acetate extraction, after water washing, add anhydrous Na
2SO
4Drying, the elimination siccative, remove behind the solvent compound (V).
Compound (V): the mol ratio of vinyl halogenation magnesium is that 1:1.1～2.9 feed intake in proportion.
Compound (V) is dissolved in the tetrahydrofuran (THF), and this liquid adds vinyl halogenation magnesium CH
2(X=Cl I) in the tetrahydrofuran solution, makes its reaction to=CH-Mg-X, continues to stir 2～8h, makes the generation (VI) that reacts completely, and adds saturated NH
4The Cl aqueous solution, the ratio of adding is: compound (V): NH
4The mass ratio of Cl is 1: 1.7, continue to stir 1～3h in room temperature, reaction is hydrolyzed, through extraction, drying, filtration, precipitation, chromatography, crystallization treatment gets white solid powdered compounds (I), continuous five step chemical reactions, do not separate once and finish, content is more than 90%, mole total recovery 83～85%.
Embodiment
Embodiment 1
The preparation of compound (III)
In the 100ml there-necked flask, add 24ml (dimethyl formamide-sherwood oil) and in-20 °～10 ℃, be added dropwise to 0.022molPCl
3, stir down adding again and be dissolved with 0.016mol eggplant Buddhist nun alcohol (II) dimethyl formamide-petroleum ether solution, continue to stir 5h, reaction is finished.Use petroleum ether extraction, water washing, oil reservoir anhydrous Na
2SO
4Drying, filtration, carrying out precipitation treatment get brown liquid, and the cooling back becomes solid chemical compound (III).
Embodiment 2
The preparation of compound (IV)
In the 100ml there-necked flask, add the methanol solution that is dissolved with the 0.027mol sodium methylate, in room temperature the 0.03mol methyl acetoacetate is added in the bottle, heat up and stir 1.5h in 30 ℃, dropping is dissolved with the petroleum ether solution of 11g (0.015mol) compound (III), heat up in 60 ℃ and stir 1～5h, reaction finish (IV).Need not handle the hydrolysis reaction that is directly used in down the step.
Embodiment 3
In the 100ml there-necked flask, add the ethanolic soln that is dissolved with the 0.027mol sodium ethylate, in room temperature the 0.03mol methyl aceto acetate is added in the bottle, heat up after finishing and stir 4h in 50 ℃, be dissolved with the sherwood oil of 11g (0.015mol) compound (III) then in 30 ℃ of addings, heat up after finishing in reflux to stir the 5h reaction finish (IV).
Embodiment 4
The preparation of compound (V)
The above-mentioned reaction mixture that contains compound (IV) is heated to backflow, adds the alkali lye that is dissolved with 0.72mol NaOH, continue stirring and refluxing 1h, reaction is finished, and uses ethyl acetate extraction, through water washing ground, anhydrous Na
2SO
4Drying, filtration, carrying out precipitation treatment get brown liquid (V).
Embodiment 5
The above-mentioned reaction mixture that contains compound (IV) is heated to backflow, adds the alkali lye that is dissolved with 0.72mol KOH, stirring and refluxing 5h reaction is finished, and uses ethyl acetate extraction, gets brown liquid (V) through washing, drying, filtration, precipitation aftertreatment.
Embodiment 6
The preparation of compound (I)
In the 100mol there-necked flask, (tetrahydrofuran solution of CH2=CH-Mg-Cl) adds the tetrahydrofuran solution that is dissolved with 10g (0.013mol) compound (V), makes its reaction, continues to stir 8h and gets (VI) to add 0.02mol Ge Shi agent.Add and be dissolved with 0.019mol NH
4The aqueous solution of Cl, hydrolysis continues to stir the 3h reaction and finishes, through extraction, washing, anhydrous MgSO
4Drying, filtration, carrying out precipitation treatment get compound isodecyl alcohol deca-isopentyl alcohol (I) crude product 12g, pass through chromatography again, with the sherwood oil wash-out of 2% ethyl acetate, obtain colourless oil liquid, through crystallization purifying handle (I) pure product of content 92.5%.
More than refining in the middle of the five step chemical reactions, a purifying, finish isodecyl alcohol deca-isopentyl alcohol, total recovery is 83～85%, content〉90%.
Claims (3)
1. a preparation method for isodeca-deca-isoprene-yl alcohol is characterized in that this method comprises the following steps:
(1) halogenating reaction prepares compound (III)
In reactor, put into dimethyl formamide-petroleum ether solvent, under-20 ℃～10 ℃ conditions, in reactor, drip PX
3, when stirring, add the eggplant Buddhist nun alcohol (II) that is dissolved in advance in dimethyl formamide-petroleum ether solvent, continue to stir 1～5h and carry out halogenating reaction, reaction is finished, and uses petroleum ether extraction, and water washing discards water layer, the oil reservoir anhydrous Na
2SO
4Drying removes by filter siccative, obtains solid chemical compound (III) after removing the liquid cooling behind the solvent;
(2) preparation compound (IV):
In reaction vessel, add the sodium alkoxide alcoholic solution, add acetylacetic ester again, be warming up to 30 ℃ and stir 1.5h, the petroleum ether solution of the compound (III) that dropping step (1) makes is warming up to 60 ℃ then and stirs 1～5h, carries out substituted condensed reaction, reaction is complete to make compound (IV), need not handle directly entering the next step;
(3) preparation compound (V):
The reaction solution that contains compound (IV) that step (2) is made is heated to backflow, adds alkaline solution, continues stirring and refluxing 1～5h, and reaction is finished, and uses ethyl acetate extraction, after water washing, adds anhydrous Na
2SO
4Drying, the elimination siccative, remove behind the solvent compound (V);
(4) preparation isodecyl alcohol deca-isopentyl alcohol (I):
Add the tetrahydrofuran solution of vinyl halogenation magnesium in reaction vessel, and then add the tetrahydrofuran solution that contains compound (V), stirring reaction 2～8h makes compound (VI) after reacting completely, and adds saturated NH in reactant
4The Cl aqueous solution, stirring at room 1～3h reaction that is hydrolyzed, reaction is finished, and uses ethyl acetate extraction, after water washing, adds anhydrous MgSO
4Drying, the elimination siccative obtains isodecyl alcohol deca-isopentyl alcohol (I) crude product behind the desolventizing, again through chromatography, the sherwood oil wash-out with 2% ethyl acetate, obtain colourless oil liquid, behind crystallization purifying content 90% pure product (I);
Reaction formula:
Wherein: PX
3In X=Cl or I;
CH
3COCH
2R ' among the COOR '=CH
3Or C
2H
5
R=CH among the RONa
3Or C
2H
5
H
2X=Cl among C=CH-MgX or I.
2. a kind of preparation method for isodeca-deca-isoprene-yl alcohol according to claim 1 is characterized in that the proportioning of compound in each step reaction is:
(1) eggplant Buddhist nun alcohol (II): PX
3Mol ratio be 1: 1.0～2.5;
(2) compound (III): acetylacetic ester: the mol ratio of sodium alkoxide is 1: 3: 2.8;
(3) compound (III): the mass ratio of alkali is 1: 2～5;
(4) compound (V): the mol ratio of vinyl halogenation magnesium is 1: 1.1～2.9;
(5) compound (V): NH
4The mass ratio of Cl is 1: 1.7.
3. a kind of preparation method for isodeca-deca-isoprene-yl alcohol according to claim 1 is characterized in that the alkali in the described alkaline solution of step (3) is NaOH or KOH.
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|---|---|---|---|
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|---|---|---|---|
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| CN100462346C true CN100462346C (en) | 2009-02-18 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100551889C (en) * | 2006-10-09 | 2009-10-21 | 昆明通发实业有限公司 | A kind of continuous medium pressure column chromatography prepares the method for high purity isodecyl alcohol deca-isopentyl alcohol |
| CN101863740B (en) * | 2010-07-02 | 2013-10-16 | 玉溪健坤生物药业有限公司 | Preparation method of decanisoprenol |
| CN106316777B (en) * | 2016-08-17 | 2019-01-08 | 巨化集团技术中心 | A kind of preparation method of 2,3,3,3- tetrafluoropropene |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1629115A (en) * | 2004-08-06 | 2005-06-22 | 昆明韬辉生物工贸有限责任公司 | Method for extraction of high purity solanocupsin and synthesis of isodecyl dienol and isoprenol |
| CN1634840A (en) * | 2004-10-14 | 2005-07-06 | 昆明韬辉生物工贸有限责任公司 | Method for synthesizing Q#-[10] by side chain coupling extension method |
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2005
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1629115A (en) * | 2004-08-06 | 2005-06-22 | 昆明韬辉生物工贸有限责任公司 | Method for extraction of high purity solanocupsin and synthesis of isodecyl dienol and isoprenol |
| CN1634840A (en) * | 2004-10-14 | 2005-07-06 | 昆明韬辉生物工贸有限责任公司 | Method for synthesizing Q#-[10] by side chain coupling extension method |
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