CN102351623B - Method for increasing optical purity of chiral alkynol - Google Patents
Method for increasing optical purity of chiral alkynol Download PDFInfo
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- CN102351623B CN102351623B CN201110224230.2A CN201110224230A CN102351623B CN 102351623 B CN102351623 B CN 102351623B CN 201110224230 A CN201110224230 A CN 201110224230A CN 102351623 B CN102351623 B CN 102351623B
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Abstract
The invention relates to the technical field of chemistry and provides a method for preparing chiral alkynol with high purity. According to esterification and recrystallization of chiral alkynol, an ee value of a chiral alkynol compound is increased. The method has advantages of simple and practical process, high conversion rate and wide applicability, etc.; the obtained R-alkynol and S-alkynol have optical purities higher than 99%. Chemical reactions in the method need simple and mild reaction conditions and simple equipment and are convenient for operation. According to the technique, optical purity of the original alkynol can be increased rapidly by simple esterification, recrystallization and hydrolysis; and an esterification product has good stability and provides guarantee for industrialized application; therefore, the method has promising industrialized application prospect.
Description
Technical field
The invention belongs to technical field of chemistry, be specifically related to a kind of method that improves optical purity of chiral alkynol.
Background technology
Optical activity alkynol be a lot of natural products and drug molecule important structure unit (1.
angewandte Chemie, International Edition 1999,
38, 711; 2.
journal of Organic Chemistry 1990, 55(25), 6223-5.).Because it comprises alkynyl and these two kinds flexible variable functional groups of hydroxyl, make it aspect molecular diversity, also there is very large potential using value.
Optical activity alkynol generally obtains by the following method: one, the fractionation of racemic modification compound, a pair of enantiomer is reacted with an optically pure chipal compounds and is formed a pair of diastereomer, then separate by crystallization or chromatographic process, but wherein a kind of enantiomer is wasted.Two, by the compou nd synthesis objective optics active compound in chiral source storehouse, the compound in chiral source storehouse typically refers to some natural optically active compounds.Although the compound cheapness in chiral source storehouse, be easy to get, its kind is limited, very large (1. to the kind restriction of synthetic target compound
tetrahedron 1999, 55(15), 4649-4654; 2.
journal of Natural Products 1999, 62(4), 626-628.).Three, obtain light chipal compounds alive (1. by the method for enzyme, cell cultures or microbial transformation
synthetic Communications 2002, 32(17), 2733-2740).Four,, via the asymmetric synthesis of prochirality compound for catalysis, the method is that at present one of most economical the most effective synthesis strategy is (1.
journal of the American Chemical S degree iety 1994,
116, 3151; 2.
synthesis 1999, 1453; 3.
journal of the American Chemical S degree iety 2006, 128(34), 10996-10997.).But based on the character of chiral catalyst itself, asymmetric catalysis has certain selectivity for reaction substrate, conventionally only have special construction could obtain higher optical purity.This patent has reported that the optical purity of the chirality alkynol with medium optical purity is increased to high optical purity by a kind of simple method, and the method have not been reported so far.
High optically pure alkynol compounds is and useful intermediate in organic synthesis always, has extremely important scientific research and industrial application value.
Summary of the invention
For these reasons, applicant by years of researches, finds unexpectedly, chirality alkynol is by the method such as esterification, recrystallization, can well improve chirality alkynol compounds
eevalue.The advantages such as it is simple that the method has process, and transformation efficiency is high, widely applicable, and obtain
r-alkynol and
sthe optical purity of-alkynol can be increased to and be greater than 99%.The chemical reaction condition that method is used is simple, reaction conditions gentleness, and easy to operate, equipment is simple.This technology only by simple esterification, recrystallization, hydrolysis just can Quick the optical purity of high original alkynol, and the good stability of esterified prod, for industrial applications provides guarantee, thereby has good prospects for commercial application.
the present invention is achieved through the following technical solutions.
A kind of method that improves optical purity of chiral alkynol, get optical purity and be greater than 80% and be less than or equal to 90% alkynol, mix with amine, organic solvent, add the organic solution of esterification acyl halide reagent, reaction obtains alkynol ester, recrystallization, obtain chirality alkynol ester, after hydrolysis, obtain the chirality alkynol that purity is greater than 99%.
Alkynol described above includes but not limited to alkyl alkynol, aryl alkynol or heterocycle alkynol.
Esterification carboxylic acid halides reagent described above includes but not limited to 3,5 dinitrobenzoylchloride, 2,4,6-trichloro-benzoyl chloride, diamantane methyl acyl chlorides, 3,5-dinitrobenzene benzoyl bromide, 2,4,6-trichlorine benzoyl bromide or diamantane methyl acylbromide.
Amine described above includes but not limited to triethylamine, Tributylamine, tri-isopropyl amine, diisopropylethylamine or xylidine.
Organic solvent described above includes but not limited to methylene dichloride, tetrahydrofuran (THF), toluene, benzene, chloroform, 1,2-ethylene dichloride, normal hexane or normal heptane.
The object of the invention is to improve the method for the high optical purity of chiral alkynol of a kind of Quick.
Preferred method is: under protection of inert gas; low optical purity alkynol, triethylamine, anhydrous methylene chloride add in reaction flask; under ice bath, slowly drip the dichloromethane solution that dissolves large steric hindrance acyl chlorides, after dropwising, naturally rise to room temperature; TLC detects; after reacting completely, under ice bath, add saturated ammonium chloride, dichloromethane extraction three times, organic phase is through anhydrous sodium sulfate drying; concentrating under reduced pressure, obtains solid.
Described alkynol can alkyl alkyl, aryl or the low optical purity alkynol of heterocyclic radical.Esterification acyl halide reagent is 3,5 dinitrobenzoylchloride, 2,4, the large steric hindrance compound of the acyl chlorides such as 6-trichloro-benzoyl chloride, diamantane methyl acyl chlorides or acylbromide.Amine is the tertiary amines such as triethylamine, Tributylamine, tri-isopropyl amine, diisopropylethylamine or xylidine.Organic solvent is methylene dichloride, tetrahydrofuran (THF), toluene, benzene, chloroform, 1, the non-proton property anhydrous solvents such as 2-ethylene dichloride, normal hexane, normal heptane.
Embodiment
The object of the invention is to improve the method for the high optical purity of chiral alkynol of a kind of Quick.It is by esterification recrystallization that the present invention produces high optical activity chiral alkynol, first obtains high optical purity alkynol ester cpds, is hydrolyzed subsequently alkynes ester and obtains high optical activity chiral alkynol.Its chemical equation is as follows:
preparation Example
embodiment 1 is high, and optically pure chirality 5-is trimethyl silicon based-preparation of 1-thiazolinyl-4-alkynyl-3-amylalcohol:
(1) preparation (
r)-5-is trimethyl silicon based-1-amylene-4-alkynes-3-amylalcohol
In 200mL reaction flask, inject 50mL anhydrous methylene chloride, be 86%ee by optical purity (
r)-5-is trimethyl silicon based-1-thiazolinyl-4-alkynyl-3-amylalcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the dichloromethane solution 20mL that dissolves 3,5 dinitrobenzoylchloride 5.53g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
r)-5-is trimethyl silicon based-1-amylene-4-alkynes-3-3, and 5-dinitrobenzoic acid ester 6.40g (18.4 mmol, 92%).
By gained (
r)-5-is trimethyl silicon based-1-amylene-4-alkynes-3-3,5-dinitrobenzoic acid ester 6.40g, be dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.48g (12.8 mmol, 70%) that obtains.
By the colourless transparent crystal 3.48g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.39g (9mmol, 90%).
Product ultimate yield 65%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 210 nm) Rention time:t
minor =7.15 min, t
major =7.46 min.) [
α]
d 20=-37.6 (
c1.3, CHCl
3)).
(2) preparation (
s)-5 are trimethyl silicon based-1-amylene-4-alkynes-3-amylalcohol
In 200mL reaction flask, inject 50mL anhydrous methylene chloride, be 86%ee by optical purity (
s)-5 are trimethyl silicon based-1-thiazolinyl-4-alkynyl-3-amylalcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the dichloromethane solution 20mL that dissolves 3,5 dinitrobenzoylchloride 5.53g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30 mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
s)-5-is trimethyl silicon based--1-amylene-4-alkynes-3-3, and 5-dinitrobenzoic acid ester 6.40g (18.4mmol, 92%).
By gained (
s)-1-amylene-4-alkynes-3-3,5-dinitrobenzoic acid ester 6.40g, is dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.48g (12.8 mmol, 70%) that obtains.
By the colourless transparent crystal 3.48g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.39g (9mmol, 90%).
Product ultimate yield 65%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 210 nm) Rention time:t
major =7.32 min, t
minor =7.67 min.) [
α]
d 20=+36.2 (
c1.3, CHCl
3)).
(3) preparation (
r)-5-is trimethyl silicon based-1-amylene-4-alkynes-3-amylalcohol
In 200mL reaction flask, inject 50mL dry toluene, be 86%ee by optical purity (
r)-5-is trimethyl silicon based-1-thiazolinyl-4-alkynyl-3-amylalcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip toluene solution 20 mL that dissolve 3,5-dinitrobenzene benzoyl bromide 6.60g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20 mL saturated ammonium chlorides after reacting completely under ice bath, toluene 30 mL extraction three times, and organic phase is through anhydrous Na
2sO
4dry, concentrating under reduced pressure, obtain light yellow solid (
r)-5-is trimethyl silicon based-1-amylene-4-alkynes-3-3, and 5-dinitrobenzoic acid ester 6.40g (18.4 mmol, 92%).
By gained (
r)-5-is trimethyl silicon based-1-amylene-4-alkynes-3-3,5-dinitrobenzoic acid ester 6.40g, be dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.48g (12.8 mmol, 70%) that obtains.
By the colourless transparent crystal 3.48g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.39g (9 mmol, 90%)
Product ultimate yield 65%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1mL/min, 210 nm) Rention time:t
minor =7.15 min, t
major =7.46 min.) [
α]
d 20=-37.6 (
c1.3, CHCl
3)).
(4) preparation (
s)-5 are trimethyl silicon based-1-amylene-4-alkynes-3-amylalcohol
In 200mL reaction flask, inject 50mL dry toluene, be 86%ee by optical purity (
s)-5 are trimethyl silicon based-1-thiazolinyl-4-alkynyl-3-amylalcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the toluene solution 20mL that dissolves 3,5 dinitrobenzoylchloride 6.60g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, toluene 30mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
s)-5 are trimethyl silicon based-1-amylene-4-alkynes-3-3, and 5-dinitrobenzoic acid ester 6.40g (18.4mmol, 92%).
By gained (
s)-1-amylene-4-alkynes-3-3,5-dinitrobenzoic acid ester 6.40g, is dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.48g (12.8 mmol, 70%) that obtains.
By the colourless transparent crystal 3.48g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.39g (9 mmol, 90%).
Product ultimate yield 65%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 210 nm) Rention time:t
major =7.32 min, t
minor =7.67 min.) [
α]
d 20=+36.2 (
c1.3, CHCl
3)).
the preparation of the high optically pure chirality 1-phenyl-2-alkynes-1-propyl alcohol of embodiment 2:
(1) preparation (
r)-1-phenyl-2-alkynes-1-propyl alcohol
In 200mL reaction flask, inject 50mL anhydrous methylene chloride, be 90%ee by optical purity (
r)-1-phenyl-2-alkynes-1-propyl alcohol 2.64g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the dichloromethane solution 20mL that dissolves 3,5 dinitrobenzoylchloride 5.53g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30 mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
r)-1-phenyl-2-propine-1-3,5-dinitrobenzoic acid ester 6.19g (18.9 mmol, 95%).
By gained (
r)-1-phenyl-2-propine-1-3,5-dinitrobenzoic acid ester 6.19g, is dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.64 (14.2 mmol, 75%) that obtains.
By the colourless transparent crystal 3.26g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.19g (9 mmol, 90%).
Product ultimate yield 73%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 254nm) Rention time:t
major =23.48min, t
minor =21.31 min. [
α]
d 20=-18.1 (
c2.3, CHCl
3)).
(2) preparation (
s)-1-phenyl-2-alkynes-1-propyl alcohol
In 200mL reaction flask, inject 50mL anhydrous methylene chloride, be 90%ee by optical purity (
s)-1-phenyl-2-alkynes-1-propyl alcohol 2.64g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the dichloromethane solution 20mL that dissolves 3,5 dinitrobenzoylchloride 5.53g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
s)-1-phenyl-2-propine-1-3,5-dinitrobenzoic acid ester 6.19g (18.9 mmol, 95%).
By gained (
s)-1-phenyl-2-propine-1-3,5-dinitrobenzoic acid ester 6.19g, is dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.64 (14.2 mmol, 75%) that obtains.
By the colourless transparent crystal 3.26g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.19g (9 mmol, 90%).
Product ultimate yield 73%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 254nm) Rention time:t
major =21.31 min, t
minor =23.48 min. [
α]
d 20=+16.0 (
c2.0, CHCl
3)).
(3) preparation (
r)-1-phenyl-2-alkynes-1-propyl alcohol
In 200mL reaction flask, inject 50mL anhydrous tetrahydro furan, be 90%ee by optical purity (
r)-1-phenyl-2-alkynes-1-propyl alcohol 2.64g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the tetrahydrofuran solution 20mL that dissolves 2,4,6-trichloro-benzoyl chloride 5.85g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30 mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
r)-1-phenyl-2-propine-1-2,4,6-trichlorobenzoic acid ester 6.27g (18.5 mmol, 93%).
By gained (
r)-1-phenyl-2-propine-1-2,4,6-trichlorobenzoic acid ester 6.27g, be dissolved in 10ml anhydrous methylene chloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.45g (13.1 mmol, 71%) that obtains.
By the colourless transparent crystal 3.39g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.19g (9 mmol, 90%).
Product ultimate yield 71%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 254nm) Rention time:t
major =23.48min, t
minor =21.31 min. [
α]
d 20=-18.1 (
c2.3, CHCl
3)).
(4) preparation (
s)-1-phenyl-2-alkynes-1-propyl alcohol
In 200mL reaction flask, inject 50mL anhydrous tetrahydro furan, be 90%ee by optical purity (
s)-1-phenyl-2-alkynes-1-propyl alcohol 2.64g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the tetrahydrofuran solution 20mL that dissolves 2,4,6-trichloro-benzoyl chloride 5.85g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30 mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
s)-1-phenyl-2-propine-1-2,4,6-trichlorobenzoic acid ester 6.27g (18.5 mmol, 93%).
By gained (
s)-1-phenyl-2-propine-1-2,4,6-trichlorobenzoic acid ester 6.27g, be dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.45g (13.1 mmol, 71%) that obtains.
By the colourless transparent crystal 3.39g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.19g (9 mmol, 90%).
Product ultimate yield 71%, optical purity from 85%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 254nm) Rention time:t
major =21.31 min, t
minor =23.48 min. [
α]
d 20=+16.0 (
c2.0, CHCl
3)).
the high optically pure chirality 1-alkynyl-3-certain herbaceous plants with big flowers alcohol of embodiment 3:
(1) preparation (
r)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol
In 200mL reaction flask, inject 50mL anhydrous methylene chloride, be 82%ee by optical purity (
r)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the dichloromethane solution 20mL that dissolves 3,5 dinitrobenzoylchloride 5.53g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
r)-1-alkynyl-3-3,5-dinitrobenzoic acid ester 6.47g (18.6 mmol, 93%).
By gained (
r)-1-alkynyl-3-3,5-dinitrobenzoic acid ester 6.47g, is dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.2g (12.0 mmol, 65%) that obtains.
By the colourless transparent crystal 3.48g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.41g (9.1 mmol, 91%).
Product ultimate yield 63%, optical purity from 82%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 210 nm) Rention time:t
major =9.45 min, t
minor =9.21 min. [
α]
d 20=+4.2 (
c1.1, CHCl
3)).
(2) preparation (
s)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol
In 200mL reaction flask, inject 50mL anhydrous methylene chloride, be 82%ee by optical purity (
s)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the dichloromethane solution 20mL that dissolves 3,5 dinitrobenzoylchloride 5.53g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, methylene dichloride 30mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
s)-1-alkynyl-3-3,5-dinitrobenzoic acid ester 6.47g (18.6 mmol, 93%).
By gained (
s)-1-alkynyl-3-3,5-dinitrobenzoic acid ester 6.47g, is dissolved in 10ml methylene dichloride, stir the lower normal hexane that slowly drips to there being muddy generation, be heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.2g (12.0 mmol, 65%) that obtains.
By the colourless transparent crystal 3.48g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.41g (9.1 mmol, 91%).
Product ultimate yield 63%, optical purity from 82%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 210 nm) Rention time:t
major =9.21 min, t
minor =9.45 min. [
α]
d 20=-3.9 (
c3.4, CHCl
3)).
(3) preparation (
r)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol
In 200mL reaction flask, inject 50mL anhydrous n-hexane, be 82%ee by optical purity (
r)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the hexane solution 20mL that dissolves diamantane formyl chloride 4.75g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, normal hexane 30mL extraction three times, organic phase is through anhydrous sodium sulfate drying, concentrating under reduced pressure, obtain light yellow solid (
r)-1-decine-3 adamantanecarboxylic acid ester 5.75g (18.2 mmol, 91%).
By gained (
r)-1-decine-3-adamantanecarboxylic acid ester 5.75g, is dissolved in 10ml methylene dichloride, stirs the lower slow normal hexane that drips to there being muddy generation, is heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.17g (13.2 mmol, 72%) that obtains.
By the colourless transparent crystal 3.16g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.41g (9.1 mmol, 91%).
Product ultimate yield 58%, optical purity from 82%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 210 nm) Rention time:t
major =9.45 min, t
minor =9.21 min. [
α]
d 20=+4.2 (
c1.1, CHCl
3)).
(4) preparation (
s)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol
In 200mL reaction flask, inject 50mL anhydrous n-hexane, be 82%ee by optical purity (
s)-1-alkynyl-3-certain herbaceous plants with big flowers alcohol 3.08g(20 mmol) and triethylamine 4.04g(40 mmol), under ice bath, slowly drip the hexane solution 20mL that dissolves diamantane formyl chloride 4.75g (24 mmol).After dropwising, naturally rise to room temperature, TLC detects, and adds 20mL saturated ammonium chloride after reacting completely under ice bath, normal hexane 30 mL extraction three times, and organic phase is through anhydrous Na
2sO
4dry, concentrating under reduced pressure, obtain light yellow solid (
s)-1-decine-3 adamantanecarboxylic acid ester 5.75g (18.2 mmol, 91%).
By gained (
s)-1-decine-3-adamantanecarboxylic acid ester 5.88g, is dissolved in 10ml methylene dichloride, stirs the lower slow normal hexane that drips to there being muddy generation, is heated to solution clarification, crystallisation by cooling, the final colourless transparent crystal 4.17g (13.2 mmol, 72%) that obtains.
By the colourless transparent crystal 3.16g(10 mmol of gained) be dissolved in 40ml tetrahydrofuran (THF), at 0 DEG C, slowly drip the aqueous sodium hydroxide solution 25ml of 2mol/L, after 30min, methylene dichloride 30ml extraction three times, anhydrous sodium sulfate drying, precipitation, obtain colourless transparent liquid 1.41g (9.1 mmol, 91%).
Product ultimate yield 58%, optical purity from 82%ee to 99.5%ee (through high-performance liquid chromatogram determination: chirality AD post (Virahol: normal hexane=2:98,1 mL/min, 210 nm) Rention time:t
major =9.21 min, t
minor =9.45 min. [
α]
d 20=-3.9 (
c3.4, CHCl
3)).
Described embodiment includes but not limited to above-mentioned.
Claims (1)
1. one kind is improved the method for optical purity of chiral alkynol, it is characterized in that: get optical purity and be greater than 80% and be less than or equal to 90% alkynol, mix with amine, organic solvent, add the organic solution of esterification acyl halide reagent, reaction obtains alkynol ester, recrystallization, obtain chirality alkynol ester, after hydrolysis, obtain the chirality alkynol that purity is greater than 99%; Wherein said alkynol is alkyl alkynol, aryl alkynol or heterocycle alkynol; Wherein said esterification acyl halide reagent is 3,5 dinitrobenzoylchloride, 2,4,6-trichloro-benzoyl chloride, diamantane methyl acyl chlorides, 3,5-dinitrobenzene benzoyl bromide, 2,4,6-trichlorine benzoyl bromide or diamantane methyl acylbromide; Wherein said amine is triethylamine, Tributylamine, tri-isopropyl amine, diisopropylethylamine or xylidine; Wherein said organic solvent is methylene dichloride, tetrahydrofuran (THF), toluene, benzene, chloroform, 1,2-ethylene dichloride, normal hexane or normal heptane.
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| 阮源萍.高效液相色谱法测定12三甲基硅基212炔232癸醇对映体纯度.《厦门大学学报(自然科学版)》.2008,第47卷(第4 期),537-540. |
| 高效液相色谱法测定12三甲基硅基212炔232癸醇对映体纯度;阮源萍;《厦门大学学报(自然科学版)》;20080731;第47卷(第4 期);537-540 * |
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