CN102532089B - Method for preparing chirality glycerol acetonide - Google Patents
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- CN102532089B CN102532089B CN201110435269.9A CN201110435269A CN102532089B CN 102532089 B CN102532089 B CN 102532089B CN 201110435269 A CN201110435269 A CN 201110435269A CN 102532089 B CN102532089 B CN 102532089B
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- BPTPYIHTQLLNDS-NQPNHJOESA-N CC(C)(OC1)O[C@@]1(C1)C1N Chemical compound CC(C)(OC1)O[C@@]1(C1)C1N BPTPYIHTQLLNDS-NQPNHJOESA-N 0.000 description 1
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Abstract
The invention relates to a method for preparing chirality glycerol acetonide. Chirality epichlorohydrin which is commercialized or easy to prepare is used as an initial raw material, and chirality glycerol acetonide is prepared through condensation, substituting and hydrolysis. The method is easy in raw material collection, high in reaction purity yield, stable in technology, easy to operate, environment-friendly, suitable for scale production after pilot plant tests and provides a novel idea and method for preparing chirality glycerol acetonide.
Description
(1) technical field:
The present invention relates to a kind of method of preparing organic synthesis intermediate, particularly a kind of method of preparing chirality glycerol acetonide.
(2) background technology:
The core texture of chirality glycerol acetonide is 1,3-dioxolane, can be used as solvent, is mainly used in grease, dyestuff, derivatived cellulose, polymer solvent, coating, tackiness agent, wax and chlorine based compound, also be used as the stablizer of trichloroethane, the component of sensitization liquid, developing solution; As the electrolytic solution of lithium disposable battery, Silk Finishing agent, sealing compound etc.
And chirality glycerol acetonide itself, as important organic synthesis intermediate, is widely used in food medicine and chemical industry.It can be used for synthesizing some chiral drugs and have the important as precursors of optically active natural product, can be used as a kind of chiral induction monomer synthesizing for chiral molecules of cheapness.As can be, for the preparation of the important activity intermediate of ofhypoglycemic medicine, corrected the metabolism disorder such as hyperglycemia and hyperlipidemia, impel the eubolism of sugar, protein and fat, alleviate the caused symptoms of metabolism disorder such as hyperglycemia etc.Therefore, develop a kind of high benefit, chirality glycerol acetonide synthesis technique is significant cheaply.
Present stage, the method for preparing this compounds mainly contains following several:
1, with the anhydrous ZnCl of Lewis acid
2as catalytic dehydrating agent, PEARLITOL 25C or L-N.F,USP MANNITOL and condensation of acetone obtain diisopropylidene condenses, then use NaIO
4oxidation scission of link is prepared chirality glyceraldehyde acetonide, finally uses NaBH
4reduction obtains chirality glycerol acetonide.This method requires harsh to reaction conditions, and oxidization-hydrogenation ratio only has 20～30%, is not suitable for scale operation.Please refer to US2004/54172
2, make alkali with pyridine; two molecule acetic anhydride condensations obtain diacetyl acetone; replace by hydrogen sodium reduction, benzyl the diacetyl compound that obtains racemization again; obtain diacetyl chipal compounds by the method that enzyme splits, finally take off benzyl, the cyclization of dimethoxy propylene, be hydrolyzed and obtain chirality glycerol acetonide by Pd/C.This method step is oversize, and uses some more expensive and responsive materials (hydrogen sodium, porcine pancreatic lipase, Pd/C), is not suitable for scale operation.Please refer to Suemune, Hiroshi; Mizuhara, Yukako; Akita, Hiroyuki; Sakai, Kiyoshi; Chemical and Pharmaceutical Bulletin; 1986; Vol.34 (8); 3440-3444
3, take D-malic acid or L MALIC ACID as raw material, after esterification, obtain glycol by borine dimethyl sulphide and sodium borohydride reduction again, glycol reacts cyclization with dimethoxy propylene and obtains ketal under PPTS katalysis, then obtains chirality glycerol acetonide by Lithium Aluminium Hydride ester reduction.This method has been used highly toxic product borine dimethyl sulphide and compound sodium borohydride and Lithium Aluminium Hydride to water sensitive, severe reaction conditions, and complicated operation, is not suitable for scale operation.Please refer to Robinson, R.Anthony; Clark, J.Stephen; Holmes, Andrew B; Journal of the American Chemical Society; 1993; Vol.115 (22); 10400-10401
(3) summary of the invention:
The object of the present invention is to provide a kind of method of preparing chirality glycerol acetonide, selecting the chiral epichlorohydrin of on market commercialization or easily preparation is initial feed, obtain chirality glycerol acetonide through condensation, replacement, hydrolysis, reaction process is referring to Fig. 2; The method raw material is easy to get, and reaction purity and yield are higher, process stabilizing, and simple to operate, environmental friendliness, is applicable to large-scale production, provides a kind of good thinking and method for preparing chirality glycerol acetonide.
Technical scheme of the present invention: a kind of method of preparing chirality glycerol acetonide, concrete preparation process is as follows:
(1) condensation: under the condition of acetone and Lewis acid existence, by-40～30 ℃ of system coolings, drip main raw material chiral epichlorohydrin, drip and finish, in-40～30 ℃ of insulation reaction; After reacting completely, rise again to 5～30 ℃, add saturated basic solution termination reaction, extraction, separatory, the concentrated chirality 3-chlorine-1,2-propylene glycol contracting acetone that obtains;
Wherein, the mol ratio of main raw material chiral epichlorohydrin and acetone is 1: 1.5～6.0; Main raw material chiral epichlorohydrin and lewis acidic mol ratio are 1: 0.01～1.0; The mol ratio of main raw material chiral epichlorohydrin and alkali is 1: 0.1～1.0;
(2) replace: under the condition of polar solvent and the existence of chirality 3-chlorine-1,2-propylene glycol contracting acetone, add halogenide, RCOOX, wherein R is alkane, rubigan or the p-nitrophenyl of H, C2～C3, and X is K or Na, is warming up to 130～150 ℃ of reactions; After reacting completely, add water and esters solvent extraction, separatory, the concentrated ester compound that obtains chirality glycerol acetonide;
Wherein, the amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and polar solvent is 1g/2～8ml; Chirality 3-chlorine-1,2-propylene glycol contracting acetone and halid mol ratio are 1: 1～6; The mol ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and RCOOX is 1: 1～6; Chirality 3-chlorine-1,2-propylene glycol contracting acetone with amount ratio be 1g/5～15ml; The amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and esters solvent is 1g/5～20ml;
(3) hydrolysis: under the condition existing at the ester compound of non-polar solvent and chirality glycerol acetonide, add 20% inorganic alkali solution, be incubated 20～40 ℃ of reactions; After reacting completely, separatory, extraction, concentrated, rectifying obtain finished product chirality glycerol acetonide;
Wherein, the ester compound of chirality glycerol acetonide and the amount ratio of non-polar solvent are 1g/0.5～6ml; The ester compound of chirality glycerol acetonide and the mol ratio of mineral alkali are 1: 1～6.
In above-mentioned said step (1), the mol ratio of main raw material chiral epichlorohydrin and acetone is 1: 2～5, main raw material chiral epichlorohydrin and lewis acidic mol ratio are 1: 0.05～0.5, and the mol ratio of main raw material chiral epichlorohydrin and alkali is 1: 0.2～0.8; Chirality 3-chloro-1 in said step (2), the amount ratio of 2-propylene glycol contracting acetone and polar solvent is 1g/3～7ml, chirality 3-chloro-1,2-propylene glycol contracting acetone and halid mol ratio are 1: 1～4, and the mol ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and RCOOX is 1: 1～4, chirality 3-chloro-1,2-propylene glycol contracting acetone with amount ratio be 1g/6～12ml, the amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and esters solvent is 1g/6～15ml; The ester compound of said chirality glycerol acetonide and the amount ratio of non-polar solvent are 1kg/0.5～5L, and the ester compound of chirality glycerol acetonide and the mol ratio of mineral alkali are 1: 1～5.
In above-mentioned steps (1), said Lewis acid is aluminum chloride, boron trifluoride ethyl ether complex, iron trichloride or columbium pentachloride; Said basic solution is sodium carbonate solution, sodium hydrogen carbonate solution, sodium hydroxide solution, potassium bicarbonate solution, potassium hydroxide solution or solution of potassium carbonate.
In above-mentioned steps (2), said polar solvent is dimethyl sulfoxide (DMSO), DMF, acetone, N,N-dimethylacetamide or acetonitrile; Said esters solvent is ethyl acetate, isopropyl acetate, butylacetate or ethyl propionate; Said halogenide is Sodium Bromide, Potassium Bromide, sodium iodide or potassiumiodide;
In above-mentioned steps (3), said non-polar solvent is acetone, benzene, toluene, tetracol phenixin or 1,2-ethylene dichloride; Said mineral alkali is potassium hydroxide, sodium hydroxide or calcium hydroxide.
In above-mentioned said step (1), the mol ratio of main raw material chiral epichlorohydrin and acetone is 1: 3～5, chiral epichlorohydrin and lewis acidic mol ratio are 1: 0.08～0.0.3, and the mol ratio of main raw material chiral epichlorohydrin and alkali is 1: 0.2～0.6; The amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and polar solvent is 1g/4～6ml in said step (2), and chirality 3-chlorine-1,2-propylene glycol contracting acetone and halid mol ratio are 1: 1～3, chirality 3-chlorine-1,2-propylene glycol contracting acetone and
mol ratio be 1: 1～3, chirality 3-chlorine-1,2-propylene glycol contracting acetone with amount ratio be 1g/7～10ml, the amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and esters solvent is 1g/8～12ml; In said step (3), the ester compound of chirality glycerol acetonide and the amount ratio of non-polar solvent are 1g/1～3ml, and the ester compound of chirality glycerol acetonide and the mol ratio of mineral alkali are 1: 1～3.
In above-mentioned steps (1), said Lewis acid is aluminum chloride, boron trifluoride ethyl ether complex or iron trichloride; Said basic solution is sodium carbonate solution, sodium hydrogen carbonate solution, sodium hydroxide solution or potassium bicarbonate solution.
In above-mentioned steps (2), said polar solvent is dimethyl sulfoxide (DMSO), DMF or N,N-dimethylacetamide; Esters solvent is ethyl acetate, isopropyl acetate or butylacetate; Said halogenide is Sodium Bromide or Potassium Bromide.
In above-mentioned steps (3), said non-polar solvent is acetone, toluene or 1,2-ethylene dichloride; Said mineral alkali is potassium hydroxide or sodium hydroxide.
In above-mentioned steps (1), said Lewis acid is boron trifluoride ethyl ether complex, and said basic solution is sodium hydrogen carbonate solution; In step (2), said polar solvent is DMF, and said esters solvent is ethyl acetate, and halogenide is Sodium Bromide; In step (3), said non-polar solvent is toluene, and said mineral alkali is sodium hydroxide.
Superiority of the present invention: 1, step of the present invention (2) adopt halogenide and
as the reagent that replaces chlorine, obtain the higher ester of purity; 2, step of the present invention (3) adopts 20% mineral alkali as hydrolytic reagent, accelerate the speed of reaction, improve the yield of reaction, wherein the yield of step (1) is 89～95%, the yield of step (2) is 50～60%, and the yield of step (3) is 85～94%; 3, raw materials used business-like raw material or the easy raw material of preparation of being of the present invention, can meet the needs of large-scale production; 4, product purity of the present invention is higher, is greater than 95%, process stabilizing, and the three wastes are less, and environmental friendliness is simple to operate, has passed through pilot scale checking, possesses the ability of large-scale production;
(4) accompanying drawing explanation:
Fig. 1: the chemical reaction step schema of preparing the method for chirality glycerol acetonide.
Fig. 2: the chemical reaction process schema of preparing the method for chirality glycerol acetonide.
Can understand more intuitively the technical scheme of foregoing invention in conjunction with Fig. 1 and Fig. 2.
(5) embodiment:
For the interval range occurring in embodiment, be because temperature in single test is with certain the floating of there will be of reaction process
Embodiment 1:
(1) preparation (S)-3-chlorine-1,2-propylene glycol contracting acetone
In 200L reactor, add 25.1kg acetone (4.0eq) and 1.53kg boron trifluoride ethyl ether complex (0.1eq), system is cooled to 0 ± 5 ℃, drip main raw material 10kg (S)-epoxy chloropropane (1eq), drip and finish, in 0 ± 5 ℃ of insulation reaction; After reacting completely, rise again to 10 ± 5 ℃, add 100kg saturated sodium bicarbonate solution (0.4eq) termination reaction, extraction, separatory, concentrated obtaining
15.5kg, yield 95%, gas phase purity (GC): 97.5%.
(2) prepare acetic acid ((S)-2,2-dimethyl-DOX-4-yl) methyl esters
To the DMF (1g/5ml) and the 15kg that add 70.5kg in 200L reactor
(1.0eq), stir, add successively 10.3kg Sodium Bromide (1.0eq), 8.2kg sodium acetate (1.0eq), be warming up to 140 ± 5 ℃ of reactions; After reacting completely, add 120kg water (1g/8ml) and 135kg ethyl acetate (1g/10ml) extraction, separatory, concentrated obtaining
10.4kg, yield 60%, gas phase purity (GC): 93%.
(3) preparation (R)-(-)-glyceryl alcohol contracting acetone
In 300L reactor, add 17.4kg toluene (1kg/2L) and 10kg
(1.0eq), stir, add sodium hydroxide (2.0eq) solution of 23kg20%, be incubated 30 ± 5 ℃ of reactions; After reacting completely, separatory, extraction, concentrated, rectifying obtain finished product (R)-(-)-glyceryl alcohol contracting acetone
7.1kg.Yield 94%, gas phase purity (GC): 98%.
Embodiment 2:
(1) preparation (S)-3-chlorine-1,2-propylene glycol contracting acetone
In 200L reactor, add 75.2kg acetone (6.0eq) and 28.8kg aluminum chloride (1eq), system is cooled to-40 ± 5 ℃, drip main raw material 20kg (S)-epoxy chloropropane (1eq), drip and finish, in-40 ± 5 ℃ of insulation reaction; After reacting completely, rise again to 20 ± 5 ℃, add 53.5kg saturated potassium hydrogen carbonate solution (1.0eq) termination reaction, extraction, separatory, concentrated obtaining
30kg, yield 92%, gas phase purity (GC): 95%.
(2) prepare 4-chloro-benzoic acid ((S)-2,2-dimethyl-DOX-4-yl) methyl esters
To the dimethyl sulfoxide (DMSO) (1g/8ml) and the 30kg that add 264kg in 1000L reactor
(1.0eq), stir, add successively 143kg Potassium Bromide (6.0eq), 213kg Sodium P-Chlorobenzoate (6.0eq), be warming up to 135 ± 5 ℃ of reactions; After reacting completely, add 450kg water (1g/15ml) and 540kg isopropyl acetate (1g/20ml) extraction, extraction, separatory, concentrated obtaining
29.7kg, yield 55%, gas phase purity (GC): 92%.
(3) preparation (R)-(-)-glyceryl alcohol contracting acetone
In 500L reactor, add 142kg acetone (1g/6ml) and 29.7kg (1.0eq)
stir, add potassium hydroxide (6.0eq) solution of 183.6kg20%, be incubated 25 ± 5 ℃ of reactions; After reacting completely, separatory, extraction, concentrated, rectifying obtain finished product (R)-(-)-glyceryl alcohol contracting acetone
13kg.Yield 90%, gas phase purity (GC): 96%.
Embodiment 3:
(1) preparation (R)-3-chlorine-1,2-propylene glycol contracting acetone
In 200L reactor, add 94kg acetone (5.0eq) and 54kg columbium pentachloride (1eq), system is cooled to 30 ± 5 ℃, drip main raw material 30kg (R)-epoxy chloropropane (1eq), drip and finish, in 30 ± 5 ℃ of insulation reaction; After reacting completely, rise again to 20 ± 5 ℃, add the saturated sodium hydroxide solution of 16kg (0.8eq) termination reaction, extraction, separatory, concentrated obtaining
43.5kg, yield 89%, gas phase purity (GC): 95.5%.
(2) prepare 4-nitrobenzoic acid ((R)-2,2-dimethyl-DOX-4-yl) methyl esters
To the acetonitrile (1g/8ml) and the 30kg that add 190kg in 1000L reactor
(1.0eq), stir, add successively 165.3kg potassiumiodide (5.0eq), 187kg p-nitrobenzoic acid potassium (5.0eq), be warming up to 130 ± 5 ℃ of reactions; After reacting completely, add 390kg water (1g/13ml) and 459kg isopropyl acetate (1g/17ml) extraction, extraction, separatory, concentrated obtaining
29.7kg, yield 53%, gas phase purity (GC): 92%.
(3) preparation (S)-(-)-glyceryl alcohol contracting acetone
In 500L reactor, add 142kg acetone (1g/5ml) and 29.7kg (1.0eq)
stir, add 20% potassium hydroxide (5.5eq) solution of 264.2kg, be incubated 25 ± 5 ℃ of reactions; After reacting completely, separatory, extraction, concentrated, rectifying obtain finished product (S)-(-)-glyceryl alcohol contracting acetone
12.1kg.Yield 87%, gas phase purity (GC): 95.5%.
Embodiment 4:
(1) preparation (S)-3-chlorine-1,2-propylene glycol contracting acetone
In 200L reactor, add 47kg acetone (1.5eq) and 0.88kg iron trichloride (0.01eq), system is cooled to-20 ± 5 ℃, drip main raw material 50kg (S)-epoxy chloropropane (1eq), drip and finish, in-20 ± 5 ℃ of insulation reaction; After reacting completely, rise again to 30 ± 5 ℃, add 20kg saturated sodium carbonate (0.1eq) solution termination reaction, extraction, separatory, concentrated obtaining
73.2kg, yield 90%, gas phase purity (GC): 91%.
(2) prepare propionic acid ((S)-2,2-dimethyl-DOX-4-yl) methyl esters
In 1000L reactor, add 136.8kgN, N-N,N-DIMETHYLACETAMIDE (1g/2ml) and 73kg
(1.0eq), stir, add successively 149.8kg Sodium Bromide (3.0eq), 140kg Sodium Propionate (3.0eq), be warming up to 145 ± 5 ℃ of reactions; After reacting completely, add 365kg water (1g/5ml) and 328kg butylacetate (1g/5ml), extraction, separatory, concentrated obtaining
45.6kg, yield 50%, gas phase purity (GC): 90%.
(3) preparation (R)-(-)-glyceryl alcohol contracting acetone
In 300L reactor, add 1 of 26.4kg, 2-ethylene dichloride (1g/0.5ml) and 45.6kg (1.0eq)
stir, add 20% calcium hydroxide (1.0eq) solution of 13.2kg, be incubated 35 ± 5 ℃ of reactions; After reacting completely, separatory, extraction, concentrated, rectifying obtain finished product (R)-(-)-glyceryl alcohol contracting acetone
27.1kg.Yield 85%, gas phase purity (GC): 95.8%.
As can be seen here, in the present invention, the disclosed method of preparing chirality glycerol acetonide can obtain the target product that purity is high, purity is stabilized in more than 95%, the raw material that synthetic method adopts is easy to get, process stabilizing, chemical reaction condition gentleness, simple to operate in whole production process, pollute lower, environmental friendliness, provides a kind of new thinking and method for preparing chirality glycerol acetonide.
Claims (10)
1. prepare a method for chirality glycerol acetonide, concrete preparation process is as follows:
(1) condensation: under the condition of acetone and Lewis acid existence, system is cooled to-40～30 ℃, drips main raw material chiral epichlorohydrin, drip and finish, in-40～30 ℃ of insulation reaction; After reacting completely, rise again to 5～30 ℃, add saturated basic solution termination reaction, extraction, separatory, the concentrated chirality 3-chlorine-1,2-propylene glycol contracting acetone that obtains;
Wherein, the mol ratio of main raw material chiral epichlorohydrin and acetone is 1:1.5～6.0; Main raw material chiral epichlorohydrin and lewis acidic mol ratio are 1:0.01～1.0; The mol ratio of main raw material chiral epichlorohydrin and alkali is 1:0.1～1.0;
(2) replace: under the condition of polar solvent and the existence of chirality 3-chlorine-1,2-propylene glycol contracting acetone, add halogenide, RCOOX, wherein R is alkane, rubigan or the p-nitrophenyl of H, C2～C3, and X is K or Na, is warming up to 130～150 ℃ of reactions; After reacting completely, add water and esters solvent extraction, separatory, the concentrated ester compound that obtains chirality glycerol acetonide;
Wherein, the amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and polar solvent is 1g/2～8ml; Chirality 3-chlorine-1,2-propylene glycol contracting acetone and halid mol ratio are 1:1～6; The mol ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and RCOOX is 1:1～6; Chirality 3-chlorine-1,2-propylene glycol contracting acetone with amount ratio be 1g/5～15ml; The amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and esters solvent is 1g/5～20ml; Said polar solvent is dimethyl sulfoxide (DMSO), DMF, acetone, N,N-dimethylacetamide or acetonitrile; Said halogenide is Sodium Bromide, Potassium Bromide, sodium iodide or potassiumiodide;
(3) hydrolysis: under the condition existing at the ester compound of non-polar solvent and chirality glycerol acetonide, add 20% inorganic alkali solution, be incubated 20～40 ℃ of reactions; After reacting completely, separatory, extraction, concentrated, rectifying obtain finished product chirality glycerol acetonide;
Wherein, the ester compound of chirality glycerol acetonide and the amount ratio of non-polar solvent are 1g/0.5～6ml; The ester compound of chirality glycerol acetonide and the mol ratio of mineral alkali are 1:1～6; Said non-polar solvent is benzene, toluene, tetracol phenixin or 1,2-ethylene dichloride.
2. according to a kind of said method of preparing chirality glycerol acetonide of claim 1, the mol ratio that it is characterized in that the middle main raw material chiral epichlorohydrin of said step (1) and acetone is 1:2～5, main raw material chiral epichlorohydrin and lewis acidic mol ratio are 1:0.05～0.5, and the mol ratio of main raw material chiral epichlorohydrin and alkali is 1:0.2～0.8; Chirality 3-chloro-1 in said step (2), the amount ratio of 2-propylene glycol contracting acetone and polar solvent is 1g/3～7ml, chirality 3-chloro-1,2-propylene glycol contracting acetone and halid mol ratio are 1:1～4, and the mol ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and RCOOX is 1:1～4, chirality 3-chloro-1,2-propylene glycol contracting acetone with amount ratio be 1g/6～12ml, the amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and esters solvent is 1g/6～15ml; The ester compound of said chirality glycerol acetonide and the amount ratio of non-polar solvent are 1kg/0.5～5L, and the ester compound of chirality glycerol acetonide and the mol ratio of mineral alkali are 1:1～5.
3. according to a kind of said method of preparing chirality glycerol acetonide of claim 1, it is characterized in that in step (1), said Lewis acid is aluminum chloride, boron trifluoride ethyl ether complex, iron trichloride or columbium pentachloride; Said basic solution is sodium carbonate solution, sodium hydrogen carbonate solution, sodium hydroxide solution, potassium bicarbonate solution, potassium hydroxide solution or solution of potassium carbonate.
4. according to a kind of said method of preparing chirality glycerol acetonide of claim 1, it is characterized in that in step (2), said esters solvent is ethyl acetate, isopropyl acetate, butylacetate or ethyl propionate.
5. according to a kind of said method of preparing chirality glycerol acetonide of claim 1, it is characterized in that in step (3), said mineral alkali is potassium hydroxide, sodium hydroxide or calcium hydroxide.
6. according to a kind of said method of preparing chirality glycerol acetonide of claim 1 or 2, the mol ratio that it is characterized in that the middle main raw material chiral epichlorohydrin of said step (1) and acetone is 1:3～5, chiral epichlorohydrin and lewis acidic mol ratio are 1:0.08～0.3, and the mol ratio of main raw material chiral epichlorohydrin and alkali is 1:0.2～0.6; The amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and polar solvent is 1g/4～6ml in said step (2), and chirality 3-chlorine-1,2-propylene glycol contracting acetone and halid mol ratio are 1:1～3, chirality 3-chlorine-1,2-propylene glycol contracting acetone and
mol ratio be 1:1～3, chirality 3-chlorine-1,2-propylene glycol contracting acetone with amount ratio be 1g/7～10ml, the amount ratio of chirality 3-chlorine-1,2-propylene glycol contracting acetone and esters solvent is 1g/8～12ml; In said step (3), the ester compound of chirality glycerol acetonide and the amount ratio of non-polar solvent are 1g/1～3ml, and the ester compound of chirality glycerol acetonide and the mol ratio of mineral alkali are 1:1～3.
7. according to a kind of said method of preparing chirality glycerol acetonide of claim 1 or 3, it is characterized in that in step (1), said Lewis acid is aluminum chloride, boron trifluoride ethyl ether complex or iron trichloride; Said basic solution is sodium carbonate solution, sodium hydrogen carbonate solution, sodium hydroxide solution or potassium bicarbonate solution.
8. according to a kind of said method of preparing chirality glycerol acetonide of claim 1 or 4, it is characterized in that in step (2), said polar solvent is dimethyl sulfoxide (DMSO), DMF or N,N-dimethylacetamide; Esters solvent is ethyl acetate, isopropyl acetate or butylacetate; Said halogenide is Sodium Bromide or Potassium Bromide.
9. according to a kind of said method of preparing chirality glycerol acetonide of claim 1 or 5, it is characterized in that in step (3), said non-polar solvent is toluene or 1,2-ethylene dichloride; Said mineral alkali is potassium hydroxide or sodium hydroxide.
10. according to a kind of said method of preparing chirality glycerol acetonide of claim 1, it is characterized in that in step (1), said Lewis acid is boron trifluoride ethyl ether complex, said basic solution is sodium hydrogen carbonate solution; In step (2), said polar solvent is DMF, and said esters solvent is ethyl acetate, and halogenide is Sodium Bromide; In step (3), said non-polar solvent is toluene, and said mineral alkali is sodium hydroxide.
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| 王朝阳等.合成左旋和右旋丙叉甘油醇的新方法.《应用化学》.2008,第25卷(第11期),1375-1377. |
| 路易斯酸盐CaCl2催化合成甘油类缩醛(酮)的研究;高珊等;《化学工程师》;20060331;第126卷(第3期);1-3 * |
| 高珊等.路易斯酸盐CaCl2催化合成甘油类缩醛(酮)的研究.《化学工程师》.2006,第126卷(第3期),1-3. |
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