CN1181027C - A kind of optically active 2,3-dienol and its synthesis method and use - Google Patents
A kind of optically active 2,3-dienol and its synthesis method and use Download PDFInfo
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- CN1181027C CN1181027C CNB011319100A CN01131910A CN1181027C CN 1181027 C CN1181027 C CN 1181027C CN B011319100 A CNB011319100 A CN B011319100A CN 01131910 A CN01131910 A CN 01131910A CN 1181027 C CN1181027 C CN 1181027C
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Abstract
The present invention prepares an optically active 2, 3-dienol compound and invents a new environmentally friendly synthesizing method of the optically active 2, 3-dienol compound. In an organic solvent, optically active propargyl alcohol reacts with paraformaldehyde, alkali and cuprous bromide to prepare the optically active 2, 3-dienol compound. The compound can be used for generating the reactions of Diels-Alder, aldol, carbonylallylation, olefindihydroxylation, etc. to prepare optically active epoxy compounds, aminoalcohol and furan derivatives.
Description
Technical field
The present invention relates to class connection enol, particularly relate to a class optical activity 2,3-joins enol, its synthetic method and purposes.
Background technology
Because optically active 2, the singularity of 3-divinyl-this body structure of 1-alcohol compound has caused this compounds to have the diversity of reaction.Therefore, this compounds is paid attention to by numerous scientist, and becomes the focus of organic chemistry research field.Document J.Am.Chem.Soc., 1990,112,878; Angew.Chem.Int.Ed.1998, disclose in 37,2392 several optically active 2, the synthetic method of 3-divinyl-1-alcohol, as
R=H, PhCH
2CH
2Or cyclohexyl, R '=Me or Et; 2 of above-mentioned synthesis of optically active, the characteristics of the method for 3-divinyl-1-alcohol are: 1) utilize the borane reagent of difficult synthetic part diphenyl ethylene diamine to make chiral reagent and aldehyde reaction prepares; 2) utilize organic propargyl tin reagent under the BINOL of chirality catalysis directly and aldehyde reaction prepare.The shortcoming of these methods is: the borane reagent synthetic route of (1) optically active diphenyl ethylene diamine is long, and has used the great toxicity organotin reagent; (2) the great toxicity organotin reagent has directly been used in reaction; (3) reactions steps that has is long; (4) reaction needed anhydrous and oxygen-free condition, operation inconvenience is unfavorable for mass production.In view of this, from environment amenable angle, perhaps the experimental implementation angle is considered, these two kinds of methods are worthless.
Summary of the invention
The problem to be solved in the present invention is that preparation is new optically active 2,3-connection enolization compound, and the invention synthesis of optically active 2, the new eco-friendly synthetic method of 3-connection enolization compound makes 2,3-connection enolization compound obtains more applications.
The present invention has synthesized the new optical activity 2 of a class, 3-connection enolization compound, and its structural formula is:
Perhaps
Wherein, R=C
1～C
5Alkyl or C
8～C
11Alkyl, and work as R=C
5H
11The time, this compound only is the S configuration; Work as R=C
8H
17The time, this compound only is the R configuration.
It is optically active 2 to the invention provides a synthetic class, the eco-friendly synthetic method of 3-connection enolization compound, and reaction formula is as follows:
In the formula, R=C
1～C
11Alkyl, aryl.
Reactions steps of the present invention can specifically describe as follows: in organic solvent, optically active propargyl alcohol and Paraformaldehyde 96, alkali, cuprous bromide stirs certain hour at a certain temperature, reaction obtains optically active 2,3-divinyl-1-alcohol, wherein the molecular formula of optically active propargyl alcohol is HC ≡ CCH (OH) R, the alkyl of R=C1～C11, aryl; Temperature of reaction is 40-140 ℃, is recommended as reflux state; Reaction times is 1-10 hour; Propargyl alcohol and Paraformaldehyde 96, the mol ratio of cuprous bromide is 1: 0.5～3: 0.1～2, be recommended as 1: 1～2: 0.1～1.Described organic solvent is C
2～C
30Ether compound, for example dioxane, glycol dimethyl ether, diethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol bisthioglycolate propyl ether, ethylene diphenyl ether, Propylene Glycol Dimethyl Ether, dipropylene glycol dme, propylene glycol dipropyl ether, propylene glycol phenyl ether, butyleneglycol dme, dibutylene glycol diethyl ether, butyleneglycol diethyl ether, butyleneglycol phenyl ether etc., described alkali is C
1～C
20Aminated compounds, for example Diisopropylamine, dibutylamine, N-methylbenzylamine, pentanoic, di-t-butyl amine etc.
For example reaction
Partial results as follows:
| R | α 20℃(in?MeOH) | Productive rate (%) | e.e.(％) |
| C 4H 9 | -17.8(c，1.00) | 60～90 | 80～99.5 |
| C 7H 15 | -16.5(c，0.95) | ||
| C 8H 17 | -19.6(c，0.95) | ||
| Ph | -130.6(c，0.95) |
Reaction
Partial results as follows:
| R | α 20℃(in?MeOH) | Productive rate (%) | e.e.(％) |
| C 4H 9 | +22.8(c，1.05) | 60～90 | 80～99.5 |
| C 7H 15 | +18.9(c，0.95) | ||
| C 8H 17 | +15.3(c，1.05) |
And the optical purity of reactant propargyl alcohol is high more, and the ee value of product is also high more.
In addition, optically active propargyl alcohol for example can import chirality by the Sharpless epoxidation, and chlorination is eliminated to reset and obtained, and perhaps uses optically active BINOL and LiAlH
4The reductive agent reduction alkynyl ketone of forming obtains.
Optical activity 2 of the present invention, the 3-connection is enols used to utilize different reaction conditionss that Diels-Alder reaction (Diels-Alder) can take place, aldol reaction (aldol), carbonyl allylation reaction (carbonylallylation), the reactions such as (olefin dihydroxylation) of alkene dihydroxylation reaction.The contriver has been developed and is utilized this compounds to prepare optically active epoxy compounds, amino alcohol, the method for furan derivative.
The present invention is first from optically active 2-alkynyl-1-alcohol, and with cuprous bromide, alkali, polyformaldehyde reaction, a step generates optically active 2,3-divinyl-1-alcohol, and simple to operate, the ee% value keeps fully, is a kind of method easily and effectively.With existing synthesis of optically active 2, the enols used method of 3-connection is compared, and has overcome the drawback of traditional method, has following characteristics: (1) has used conventional common organic reagent, has avoided the great toxicity organotin reagent.(2) reaction does not need strict anhydrous and oxygen-free, and easy and simple to handle, aftertreatment is more convenient.(3) conversion unit is simple, is easy to suitability for industrialized production.
Following examples help to understand the present invention, but are not limited to content of the present invention:
Embodiment 1
Get a clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 96mg (3.2mmol) Paraformaldehyde 96 splashes into 242mg (2.4mmol, 0.34ml) Diisopropylamine; add 264mg (2.0mmol) optical activity (S) 3-phenyl-1-propine-3-alcohol (ee%=97%); 3.0ml 1,4-dioxane, oil bath heating (120 ℃ of oil temperature); stirring and refluxing 2 hours; stop heating, be cooled to room temperature, obtain the chocolate dope; be transferred in the 100ml flask after the ether dilution; solvent 1 is sloughed in decompression, behind the 4-dioxane, adds an amount of column chromatography silica gel; after the ether dilution; decompression is spin-dried for into solid, crosses post (sherwood oil: ethyl acetate=10: 1) get product (S)-1-phenyl-2,3-divinyl-1-alcohol 182mg; ee% value 97%, productive rate 69%.
1HNMR(CDCl
3)：7.36～7.20(m，5H)，5.39(q，J＝6.5Hz，1H)，5.23(s，1H)，4.87(d，J＝6.6Hz，2H)，2.10(s，1H)
IR(neat)：3361，1956，850，700(cm
-1).
MS：m/e145(M
+-1)，129.
Embodiment 2
One clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 96mg (3.2mmol) Paraformaldehyde 96 splashes into 242mg (2.4mmol, 0.34ml) Diisopropylamine; add 264mg (2.0mmol) optical activity (R)-3-phenyl-1-propine-3-alcohol (ee%=96%); 3.0ml 1,4-dioxane, oil bath heating (120 ℃ of oil temperature); stirring and refluxing 2 hours; stop heating, be cooled to room temperature, obtain the chocolate dope; be transferred in the 100ml flask after the ether dilution; solvent 1 is sloughed in decompression, behind the 4-dioxane, adds an amount of column chromatography silica gel; after the ether dilution; decompression is spin-dried for into solid, crosses post (sherwood oil: ethyl acetate=10: 1) get product (R)-1-phenyl-2,3-divinyl-1-alcohol 225mg; ee% value 96%, productive rate 77%.
1HNMR(CDCl
3)：7.36～7.20(m，5H)，5.39(q，J＝6.5Hz，1H)，5.23(s，1H)，4.87(d，J＝6.6Hz，2H)，2.10(s，1H).
IR(neat)：3361，1956，850，700(cm
-1).
MS：m/e?145(M
+-1)，129.
Embodiment 3
Get a clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 144mg (4.8mmol) Paraformaldehyde 96; (3.6mmol, 0.51ml) Diisopropylamine add 336mg (3.0mmol) optical activity (R)-1-heptyne-3-alcohol (ee%=97%) to splash into 364mg; 4.0ml 1; the 4-dioxane, oil bath heating (120 ℃ of oil temperature), stirring and refluxing 2 hours; stop heating; be cooled to room temperature, obtain the chocolate dope, be transferred in the 100ml flask after the ether dilution; solvent 1 is sloughed in decompression; behind the 4-dioxane, add an amount of column chromatography silica gel, after the ether dilution; decompression is spin-dried for into solid; (sherwood oil: ethyl acetate=10: 1) get product 242mg, the ee% value is 97%, and productive rate is 64% to cross post.
1HNMR(CDCl
3)：5.23(q，J＝6.5Hz，1H)，4.84(d，J＝6.6Hz，2H)，4.16(s，1H)，1.57～1.53(m，2H)，1.39～1.18(m，4H)，0.89(t，J＝6.93Hz，3H).
IR(neat)：3360，1957，842(cm
-1).
MS：m/e?126(M
+)，87，69，57，41.
Embodiment 4
Get a clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 144mg (4.8mmol) Paraformaldehyde 96; (3.6mmol, 0.51ml) Diisopropylamine add 224336mg (3.0mmol) optical activity (S)-1-heptyne-3-alcohol (ee%=80%) to splash into 364mg; 3.0ml 1; the 4-dioxane, oil bath heating (120 ℃ of oil temperature), stirring and refluxing 2 hours; stop heating; be cooled to room temperature, obtain the chocolate dope, be transferred in the 100ml flask after the ether dilution; solvent 1 is sloughed in decompression; behind the 4-dioxane, add an amount of column chromatography silica gel, after the ether dilution; decompression is spin-dried for into solid; (sherwood oil: ethyl acetate=10: 1) get product 299mg, the ee% value is 80%, and productive rate is 79% to cross post.
1HNMR(CDCl
3)：5.23(q，J＝6.5Hz，1H)，4.84(d，J＝6.6Hz，2H)，4.16(s，1H)，1.57～1.53(m，2H)，1.39～1.18(m，4H)，0.89(t，J＝6.93Hz，3H).IR(neat)：3360，1957，842(cm
-1).
MS：m/e?126(M
+)，87，69，57，41.
Embodiment 5
Get a clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 96mg (3.2mmol) Paraformaldehyde 96; (2.4mmol, 0.34ml) Diisopropylamine add 308mg (2.0mmol) optical activity (R)-3-heptyl-1-propine-3-alcohol (ee%=89%) to splash into 242mg; 3.5ml 1; the 4-dioxane, oil bath heating (120 ℃ of oil temperature), stirring and refluxing 2 hours; stop heating; be cooled to room temperature, obtain the chocolate dope, be transferred in the 100ml flask after the ether dilution; solvent 1 is sloughed in decompression; behind the 4-dioxane, add an amount of column chromatography silica gel, after the ether dilution; decompression is spin-dried for into solid; (sherwood oil: ethyl acetate=10: 1) get product 234mg, the ee% value is 89%, and productive rate is 70% to cross post.
1HNMR(CDCl
3)：5.24(q，J＝6.5Hz，1H)，4.86(d，J＝6.6Hz，2H)，4.16(s，1H)，1.70～1.53(m，2H)，1.39～1.18(m，10H)，0.89(t，J＝6.93Hz，3H).
IR(neat)：
3345，1957，842(cm
-1).
MS：m/e
169(M
++1)，109，95，81，69.
Embodiment 6
One clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 96mg (3.2mmol) Paraformaldehyde 96; (2.4mmol, 0.34ml) Diisopropylamine add 308mg (2.0mmol) optical activity (S)-3-heptyl-1-propine-3-alcohol (ee%=92%) to splash into 242mg; 3.5ml 1; the 4-dioxane, oil bath heating (120 ℃ of oil temperature), stirring and refluxing 2 hours; stop heating; be cooled to room temperature, obtain the chocolate dope, be transferred in the 100ml flask after the ether dilution; solvent 1 is sloughed in decompression; behind the 4-dioxane, add an amount of column chromatography silica gel, after the ether dilution; decompression is spin-dried for into solid; (sherwood oil: ethyl acetate=10: 1) get product 266mg, the ee% value is 92%, and productive rate is 79% to cross post.
1HNMR(CDCl
3)：5.24(q，J＝6.5Hz，1H)，4.86(d，J＝6.6Hz，2H)，4.16(s，1H)，1.70～1.53(m，2H)，1.39～1.18(m，10H)，0.89(t，J＝6.93Hz，3H).
IR(neat)：3345，1957，842(cm
-1).
MS：m/e?169(M
++1)，109，95，81，69.
Embodiment 7
One clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 96mg (3.2mmol) Paraformaldehyde 96; (2.4mmol, 0.34ml) Diisopropylamine add 331mg (2.0mmol) optical activity (R)-3-octyl group-1-propine-3-alcohol (ee%=94%) to splash into 242mg; 3.0ml1; the 4-dioxane, oil bath heating (120 ℃ of oil temperature), stirring and refluxing 2 hours; stop heating; be cooled to room temperature, obtain the chocolate dope, be transferred in the 100ml flask after the ether dilution; solvent 1 is sloughed in decompression; behind the 4-dioxane, add an amount of column chromatography silica gel, after the ether dilution; decompression is spin-dried for into solid; (sherwood oil: ethyl acetate=10: 1) get product 248mg, the ee% value is 97%, and productive rate is 69% to cross post.
1HNMR(CDCl
3)：5.18(q，J＝6.5Hz，1H)，4.79(d，J＝6.7Hz，2H)，4.10(s，1H)，1.54～1.44(m，2H)，1.38～1.21(m，12H)，0.81(t，J＝6.71Hz，3H).
IR(neat)：3344，1957，842(cm
-1).
MS：m/e?183(M
++1)，109，95，69，57.
Embodiment 8
One clean reaction tubes (a built-in magnetic stick); protection of inert gas adds 94mg (0.66mmol) cuprous bromide down; 96mg (3.2mmol) Paraformaldehyde 96; splash into 2.4mmol dibutylamine or N-methylbenzylamine; add 336mg (2.0mmol) optical activity (S)-3-octyl group-1-propine-3-alcohol (ee%=96%); 3.0ml glycol dimethyl ether or diethylene glycol dimethyl ether; 40 ℃ were reacted 6 hours down, stopped heating, were cooled to room temperature; obtain the chocolate dope; be transferred in the 100ml flask after the ether dilution, solvent 1 is sloughed in decompression, behind the 4-dioxane; add an amount of column chromatography silica gel; after the ether dilution, decompression is spin-dried for into solid, crosses post (sherwood oil: ethyl acetate=10: 1) get product 262mg; the ee% value is 95%, and productive rate is 72%.
1HNMR(CDCl
3)：5.18(q，J＝6.5Hz，1H)，4.79(d，J＝6.7Hz，2H)，4.10(s，1H)，1.54～1.44(m，2H)，1.38～1.21(m，12H)，0.81(t，J＝6.71Hz，3H).
IR(neat)：3344，1957，842(cm
-1).
MS：m/e?183(M
++1)，109，95，69，57.
Claims (6)
1. a class is optically active 2, and 3-connection enolization compound is characterized in that structural formula is:
Perhaps
Wherein, R '=C
1～C
5Alkyl or C
8～C
11Alkyl, and work as R '=C
5H
11The time, this compound only is
The S configuration; Work as R '=C
8H
17The time, this compound only is the R configuration.
2. a class is optically active 2, and the eco-friendly synthetic method of 3-connection enolization compound is characterized in that reaction formula is as follows:
In the formula, R=C
1～C
11Alkyl, aryl, it is in organic solvent, molecular formula is that optically active propargyl alcohol and Paraformaldehyde 96, alkali, the cuprous bromide of HC ≡ CCH (OH) R obtained optically active 2 in 1-10 hour 40-140 ℃ of reaction, 3-divinyl-1-alcohol, the mol ratio of propargyl alcohol and Paraformaldehyde 96, cuprous bromide are 1: 0.5～3: 0.1～2.
3. a class as claimed in claim 2 is optically active 2, and the eco-friendly synthetic method of 3-connection enolization compound is characterized in that described organic solvent is C
2～C
30Ether.
4. a class as claimed in claim 2 is optically active 2, and the eco-friendly synthetic method of 3-connection enolization compound is characterized in that described alkali is C
1～C
20Amine.
5. a class as claimed in claim 2 is optically active 2, the eco-friendly synthetic method of 3-connection enolization compound, and the mol ratio that it is characterized in that propargyl alcohol and Paraformaldehyde 96, cuprous bromide is 1: 1～2: 0.1～1.
6. a class as claimed in claim 1 is optically active 2, and the purposes of 3-connection enolization compound is characterized in that being used to prepare optically active epoxy compounds, amino alcohol, furan derivatives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011319100A CN1181027C (en) | 2001-10-12 | 2001-10-12 | A kind of optically active 2,3-dienol and its synthesis method and use |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011319100A CN1181027C (en) | 2001-10-12 | 2001-10-12 | A kind of optically active 2,3-dienol and its synthesis method and use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1351984A CN1351984A (en) | 2002-06-05 |
| CN1181027C true CN1181027C (en) | 2004-12-22 |
Family
ID=4670966
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|---|---|---|---|
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1304346C (en) * | 2002-06-25 | 2007-03-14 | 中国科学院上海有机化学研究所 | Optically active 2,3-dienol and dienol ester and their synthesis and use |
| CN101503339B (en) * | 2009-03-17 | 2011-11-09 | 浙江大学 | Method for synthesizing optical activity 2,3-allenes secondary alcohol |
| CN102617261B (en) * | 2012-03-09 | 2014-10-22 | 扬州大学 | Synthesis method of cyclopropyl allene derivatives |
| CN102775268B (en) * | 2012-07-12 | 2015-05-27 | 浙江工业大学 | Preparation method of 1-methyl-1-phenyl-3-phenylpropadiene compounds |
| CN103570482B (en) * | 2012-08-09 | 2016-06-08 | 北京大学 | A kind of 1,3-bis-replaces the preparation method of allenic compound |
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2001
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