CN103483170A - Method for resolving chiral diketone compound - Google Patents
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- CN103483170A CN103483170A CN201310438421.8A CN201310438421A CN103483170A CN 103483170 A CN103483170 A CN 103483170A CN 201310438421 A CN201310438421 A CN 201310438421A CN 103483170 A CN103483170 A CN 103483170A
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Abstract
The invention discloses a method for resolving a chiral diketone compound. The method is characterized in that a 2,3:6,7-dibenzo bicyclo [3.3.1] octane-2,6-diene-4,8-dione racemate and R-1,1'-bi-2-naphthol or S-1,1'-bi-2-naphthol is used as a substrate, toluene is used as a solvent, reaction is performed at the temperature of 15-35 DEG C for 1-24 hours, filtration is carried out, a sodium hydroxide aqueous solution is used for washing a solid and a mother liquor respectively, toluene is used for extraction, and an organic phase is concentrated; the obtained solid is subjected to recrystallization by using ethyl acetate to obtain a compound with the largest ee value of 99.9%. According to the method, direct resolving of the diketone compound is realized, the total productivity of R- and S-chiral diketone with the ee value of more than 99.9% is 55% through resolving for one time, and far exceeds the total productivity of 17% recorded in a document.
Description
Technical field
The invention belongs to the method for splitting technical field of chiral ketone compounds, be specifically related to split 2,3:6 by the interaction of hydrogen bond, 7-dibenzo dicyclo [3.3.1] suffering-2,6-diene-4, the method for 8-diketone raceme.
Background technology
According to Germany's " chirality " (CHIRALITY, 2004,16:614-624) the middle introduction, for chirality 2,3:6,7-dibenzo dicyclo [3.3.1] suffering-2,6-diene-4, the acquisition of 8-diketone (abbreviation diketone), only have at present a kind of method,, to the precursor 2 of synthetic this compound, 4-phenylbenzene pentanedioic acid carries out chiral separation: at first will be to its raceme 2,4-phenylbenzene pentanedioic acid recrystallization is repeatedly to remove mesomeride wherein, and then the employing quinine is split resulting racemic modification; Adopt the resulting chirality 2 of this method, the productive rate of 4-phenylbenzene pentanedioic acid only has 17.6%, and the ee value also only has 73%; Obtaining chirality 2, after 4-phenylbenzene pentanedioic acid, then by the synthetic diketone of Fu Ke (Friedel-Crafts) reaction, then diketone is being carried out to the dione compounds that recrystallization obtains chirality; Resulting like this chirality dione compounds overall yield only has 13.5%, ee value also only to have 97%.Although aforesaid method can obtain R that the ee value is 97% and the chirality dione compounds of S type from 2,4-phenylbenzene pentanedioic acid, overall yield only has 17%, takes time and effort, and efficiency is extremely low, and cost is higher.
Summary of the invention
A kind of method that the purpose of this invention is to provide resolving chiral dione compounds, obtain the optical compounds that the ee value reaches 57%-98%, the higher chirality 2 that obtains ee value 99.9% after recrystallization, 3:6,7-dibenzo dicyclo [3.3.1] suffering-2,6-diene-4,8-dione compounds.
The method of resolving chiral dione compounds of the present invention, the mixed in molar ratio that elder generation presses 1:2:2 to methylene iodide, benzyl cyanide and Powdered sodium hydroxide is even, 145 ℃ the reaction 2 hours after, be cooled to room temperature, ratio according to every mole of methylene iodide adapted 125mL ether and 125mL water is diluted, then according to the ratio extracted with diethyl ether of every mole of methylene iodide adapted 250mL ether, the organic phase anhydrous sodium sulfate drying, filter, the benzyl cyanide that distillation is removed ether and do not reacted completely, obtain compound 2,4-phenylbenzene trimethylene cyanide, according to every gram 2, the ratio of the potassium hydroxide aqueous solution of 4-phenylbenzene trimethylene cyanide adapted 10mL ethanol and 10mL5mol/L is by 2, 4-phenylbenzene trimethylene cyanide mixes with ethanol and potassium hydroxide aqueous solution, after reflux 16 hours, cool to room temperature, ethanol is removed in distillation, by every gram 2, the ratio of 4-phenylbenzene trimethylene cyanide adapted 2mL ether is washed with ether, water is acidified to PH<7 with concentrated hydrochloric acid, by every gram 2, the ratio of 4-phenylbenzene trimethylene cyanide adapted 4mL ethyl acetate is extracted with ethyl acetate water, extraction obtains the organic phase anhydrous sodium sulfate drying, filter, ethyl acetate is removed in distillation, product is 2, 4-phenylbenzene pentanedioic acid, by every gram 2, the ratio of 4-phenylbenzene pentanedioic acid adapted vitriol oil 2mL is by 2,4-phenylbenzene pentanedioic acid and the vitriol oil mix, be heated to 85 ℃, react after 2 hours, by every gram 2, the ratio of 4-phenylbenzene pentanedioic acid adapted 10 gram ice, reaction solution is poured in ice, by every gram 2, the ratio of 4-phenylbenzene pentanedioic acid adapted toluene 6mL extracts with toluene, and organic phase alkalizes with saturated sodium bicarbonate aqueous solution, to PH>7, then use the saturated common salt water washing, anhydrous sodium sulfate drying, filter, toluene is removed in distillation, obtains structural formula and is
2,3:6,7-dibenzo dicyclo [3.3.1] is hot-2,6-diene-4,8-diketone, it is characterized in that: with structural formula, be
r-1,1'-union-2-naphthol or structural formula are
s-1, the 1'-union-2-naphthol to this 2,3:6,7-dibenzo dicyclo [3.3.1] hot-2,6-diene-4, the 8-diketone carries out chiral separation, presses mole proportioning of 0.5~1:1 by 1,1'-union-2-naphthol and 2,3:6,7-dibenzo dicyclo [3.3.1] suffering-2,6-diene-4, the 8-diketone mixes, make solvent with toluene or ethyl acetate, control 2,3:6,7-dibenzo dicyclo [3.3.1] hot-2,6-diene-4, the reaction density of 8-diketone is 0.1-0.33mol/L, mixes, 15-35 ℃ of reaction, after 1-24 hour, filter, the gained solid is mixed with toluene or the ethyl acetate solvent of equal volume again, the mixture obtained is washed by the aqueous sodium hydroxide washes of 1-5mol/L, after concentrated organic phase, obtain solid product, the employing ethyl acetate is recrystallization solvent, resulting solid product is carried out to recrystallization, obtain configuration that the ee value is higher with use 1, the dione compounds that 1'-union-2-naphthol configuration is contrary, again to the resulting mother liquor of aforementioned filtration, after washing by the aqueous sodium hydroxide washes of 1-5mol/L, concentrated organic phase, obtain solid product, the employing ethyl acetate is recrystallization solvent, the solid product obtained is carried out to recrystallization, obtain configuration that the ee value is higher with use 1, the dione compounds that 1'-union-2-naphthol configuration is identical.
In the invention described above method, described toluene or ethyl acetate solvent can be preferably toluene; Resolution reagent R-1,1 '-union-2-naphthol or S-1, the mol ratio of 1'-union-2-naphthol and raceme diketone can be preferably 0.6:1; Can in temperature of reaction, be preferably 25 ℃ of reactions 6 hours; The volumetric molar concentration of raceme diketone can be preferably 0.2mol/L.
The present invention, due to the method adopted by the interaction resolving chiral dione compounds of hydrogen bond, has realized first by 2,3:6,7-dibenzo dicyclo [3.3.1] suffering-2, and 6-diene-4, the 8-diketone splits out from its raceme.In the past bibliographical information obtain this chirality dione compounds must be to the precursor 2 of synthetic this compound, 4-phenylbenzene pentanedioic acid carries out chiral separation, the resulting chirality 2 of this method, 4-phenylbenzene pentanedioic acid productive rate only has 17.6%, the ee value also only has 73%, also will carry out step Fu Ke (Friedel-Crafts) reaction and just can obtain dione compounds, and, for mesomeride 2,4-phenylbenzene pentanedioic acid can not be utilized.According to the method in document, obtain the R of ee value 97% and the dione compounds overall yield of S type only has 17% from 2,4-phenylbenzene pentanedioic acid, so the method takes time and effort, utilization ratio is lower, and cost is higher; And adopt the inventive method directly diketone to be split, once split and can be the highest with 49% productive rate, ee value more than 73%, obtain the dione compounds of S type, and the highest dione compounds that obtains the R type with 68% productive rate, ee value more than 57%.From 2,4-phenylbenzene pentanedioic acid synthetic 2,3:6,7-dibenzo dicyclo [3.3.1] hot-2,6-diene-4, the 8-diketone, more once split, the overall yield of chirality diketone that obtains the R of ee value more than 99% and S type is the highest can reach 55%, considerably beyond the prior art of bibliographical information 17% the overall yield that can reach.Adopt method of the present invention, aqueous sodium hydroxide washes is washed to the water obtained and be acidified to PH<7 with the hydrochloric acid soln of 3%-37%, filter, productive rate with the highest 97% reclaims R-1,1'-union-2-naphthol or S-1,1'-union-2-naphthol, and R-1,1'-union-2-naphthol or S-1, the ee value of 1'-union-2-naphthol, with identical before reaction, do not affect and reuses.
Embodiment
Embodiment 1:
In the present embodiment, at first with reference to Germany's " chirality " (CHIRALITY, 2004,16:614-624) in the method for disclosed synthetic diketone, prepare structural formula and be
2,3:6,7-dibenzo dicyclo [3.3.1] is hot-2,6-diene-4, the 8-diketone, then take structural formula as
2,3:6,7-dibenzo dicyclo [3.3.1] is hot-2,6-diene-4, the 8-diketone is the method that raw material is implemented the interaction resolving chiral dione compounds that passes through hydrogen bond that the present invention proposes.The methylene iodide used, benzyl cyanide, R-1,1 '-union-2-naphthol, S-1,1 '-union-2-naphthol and Powdered sodium hydrate solid can directly be bought from reagent company.
Get 214g(0.8mol) methylene iodide, 187g(1.6mol) benzyl cyanide and 64g(1.6mol) Powdered sodium hydroxide mixes, 145 ℃ the reaction 2 hours after, be cooled to room temperature, add ether that volume ratio is 1:1 and the mixing solutions 200mL of water, by extracted with diethyl ether 3 times, each ether 200mL that uses, the organic phase anhydrous sodium sulfate drying, filter, the benzyl cyanide that distillation is removed ether and do not reacted completely, obtain 2,4-phenylbenzene trimethylene cyanide; By 110g2,4-phenylbenzene trimethylene cyanide joins in the mixing solutions of the potassium hydroxide aqueous solution of 1.1L5mol/L and 1.1L ethanol, and reflux is after 16 hours, cool to room temperature, ethanol is removed in distillation, with ether washing 4 times, use ether 220mL, water to add concentrated hydrochloric acid to be acidified to PH<7 at every turn, be extracted with ethyl acetate water 3 times, each ethyl acetate 440mL that uses, extraction obtains the organic phase anhydrous sodium sulfate drying, filters, and ethyl acetate is removed in distillation, product is 2,4-phenylbenzene pentanedioic acid; By 5g2,4-phenylbenzene pentanedioic acid and the 10mL vitriol oil mix, and are heated to 85 ℃, react after 2 hours, pour into while hot in 50g ice, with toluene extraction 3 times, use toluene 30mL at every turn, organic phase alkalizes to PH with saturated sodium bicarbonate aqueous solution>7, the saturated common salt water washing once, is then used anhydrous sodium sulfate drying, filters, toluene is removed in distillation, obtains structure and is
raceme 2,3:6,7-dibenzo dicyclo [3.3.1] is hot-2,6-diene-4,8-diketone.
Then, get raceme 2,3:6,7-dibenzo dicyclo [3.3.1] is hot-2,6-diene-4,8-diketone 12.4g(50mmol) and structure be
r-1,1 '-union-2-naphthol 8.5g(30mmol) be placed in the 500mL round-bottomed flask, add 250mL toluene (reaction density of diketone is 0.2mol/L), 25 ℃ were stirred after 12 hours, filter, with a small amount of toluene solution washing solid, resulting solid is mixed with 250mL toluene, and aqueous sodium hydroxide solution 250mL is used in the mixture obtained 1-5mol/L NaOH solution washing 3 times at every turn, water with the back extraction of 100mL toluene once, the organic phase of dissolving and extraction obtains is merged, use anhydrous sodium sulfate drying, filter, toluene is removed in distillation, obtains structure and is
the solid diketone 6.03g of S configuration, ee value 95%, then by ethyl acetate to the solid diketone recrystallization of gained S configuration once, obtain the solid diketone of 4.37gS configuration, ee value 99.9%; After reaction finishes, filter and mother liquid obtainedly wash 3 times with 1-5mol/L NaOH solution, use aqueous sodium hydroxide solution 250mL at every turn, water with the back extraction of 100mL toluene once, merges the organic phase after the mother liquor after washing and extraction, uses anhydrous sodium sulfate drying, filter, toluene is removed in distillation, obtains structure and is
the solid diketone 6.37g of R configuration, ee value 80%, then by ethyl acetate to the solid diketone recrystallization of gained R configuration once, obtain the solid diketone of 4.55gR configuration, ee value 99.9%; With the above-mentioned water obtained of washing by aqueous sodium hydroxide washes of the hydrochloric acid soln acidifying of 3%-37%, to PH<7, filter, reclaim solid, the dry 8.25g R-1 that obtains, 1 '-union-2-naphthol, productive rate is that 97%, ee value is 99%.
Embodiment 2:
In the situation that the step in same embodiment 1 and other condition are substantially constant, get raceme 2 in the present embodiment, 3:6, 7-dibenzo dicyclo [3.3.1] hot-2, 6-diene-4, 8-diketone 0.248g(1mmol) and R-1, 1 '-union-2-naphthol 0.170g(0.6mmol) be placed in the 10mL round-bottomed flask, add 5mL toluene (reaction density of diketone is 0.2mol/L), 15 ℃ are stirred 12 hours, filter, with a small amount of toluene solution washing solid, resulting solid is mixed with 5mL toluene, the mixture obtained 1-5mol/L NaOH solution washing 3 times, each aqueous sodium hydroxide solution 5mL that uses, water with the back extraction of 2mL toluene once, the organic phase of dissolving and extraction obtains is merged, use anhydrous sodium sulfate drying, filter, toluene is removed in distillation, obtain the solid diketone 0.120g of S configuration, ee value 95%, again by ethyl acetate to the solid diketone recrystallization of gained S configuration once, obtain the solid diketone of 0.080g S configuration, ee value 99.9%, after reaction finishes, filtration is mother liquid obtained washes 3 times with 1-5mol/L NaOH solution, each aqueous sodium hydroxide solution 5mL that uses, water with the back extraction of 2mL toluene once, merges the organic phase after the mother liquor after washing and extraction, use anhydrous sodium sulfate drying, filter, toluene is removed in distillation, obtains the solid diketone 0.128g of R configuration, ee value 80%, by ethyl acetate to the solid diketone recrystallization of gained R configuration once, obtain the solid diketone of 0.084g R configuration, ee value 99.9% again.
Embodiment 3:
Reference example 2, other condition is substantially constant; In the present embodiment, when when in embodiment 2, temperature of reaction changes 35 ℃ into, obtain the solid diketone 0.123g of the S configuration of ee value 82% from precipitation, then by ethyl acetate to the solid diketone recrystallization of gained S configuration once, obtain the solid diketone of 0.088g S configuration, ee value 99.9%; Obtain the solid diketone 0.125g of the R configuration of ee value 74% from mother liquor, then by ethyl acetate to the solid diketone recrystallization of gained R configuration once, obtain the solid diketone of 0.084g R configuration, ee value 99.9%.
Embodiment 4:
Reference example 2, other condition is substantially constant, and in the present embodiment, as the R-1 in embodiment 2,1 '-union-2-naphthol replaces to structure and is
s-1, during 1 '-union-2-naphthol, from precipitation, obtain structure and be
the solid diketone 0.121g of R configuration, ee value 95%, then by ethyl acetate to the solid diketone recrystallization of gained R configuration once, obtain the solid diketone of 0.089g R configuration, ee value 99.9%; Obtaining structure from mother liquor is
the solid diketone 0.126g of S configuration, ee value 78%, then by ethyl acetate to the solid diketone recrystallization of gained S configuration once, obtain the solid diketone of 0.091g S configuration, ee value 99.9%.
Embodiment 5:
In the present embodiment, with reference to the basic step in embodiment 2 and implementation condition, be the experiment 1-15 of cited conclusion in following form 1, concluded the impact of the consumption of resolution solvent, fractionation time and chiral selectors on resolution yield and ee value.
The impact of the consumption of table 1, resolution solvent, fractionation time and chiral selectors on resolution yield and ee value
The situation that affects according to the consumption of the cited resolution solvent provided of upper table 1, fractionation time and chiral selectors on resolution yield and ee value, can conclude comparative analysis as follows:
Wherein, experiment 1-3, when with ethyl acetate, making solvent, when the reaction density of diketone is 0.33mol/L, change R-1, the mol ratio of 1 '-union-2-naphthol and diketone, experimental result shows, when the ee value of chirality dione compounds is higher, productive rate is on the low side, and when productive rate is higher, the ee value is on the low side;
Experiment 4-5, when with ethyl acetate and toluene mixing solutions, making solvent, when the reaction density of diketone is 0.25mol/L, change the ratio of ethyl acetate and toluene, and result shows that the productive rate of chirality diketone product and ee value are along with the increase of toluene level has the trend of growth;
Experiment 7-8, while reducing the reaction density of diketone, result shows the productive rate of chirality dione compounds and the trend that the ee value has reduction;
Experiment 5-6, and test 7, and experiment 9-12, when changing R-1, during the mol ratio of 1 '-union-2-naphthol and diketone, show that 0.6:1 is condition preferably;
Experiment 13-15, when changing the reaction times, show that reaction times 1-24 hour is condition preferably.
Illustrate: although in above-mentioned table 1, the chiral selectors of cited employing is R-1, 1 '-union-2-naphthol, do not enumerate and use S-1, the situation of 1 '-union-2-naphthol, but in fact two kinds of reagent can reach same effect, this is because R-1, 1 '-union-2-naphthol and the diketone symmetry coupling that is configured as the S type, their effects by hydrogen bond in used solvent are piled up in order, be combined into new title complex, new title complex solubleness in used solvent is low, thereby the form with solid is separated out, and the diketone of R configuration and R-1, 1 '-union-2-naphthol symmetry is not mated, they can not pile up in order by the effect of hydrogen bond in used solvent, therefore can not separate out with the form of precipitation, accordingly, S-1, the dione compounds symmetry coupling of 1 '-union-2-naphthol and R configuration, their effects by hydrogen bond in used solvent are piled up in order, be combined into new title complex, new title complex solubleness in used solvent is low, thereby separates out with the form of solid, just as described in example 4 above, when using S-1, when 1 '-union-2-naphthol is resolution reagent, what from precipitation, obtain is the solid diketone of R configuration, and what from mother liquor, obtain is the solid diketone of S configuration.So, use 1 of isomorphism type not, 1 '-union-2-naphthol can reach the effect of fractionation as resolution reagent, and its difference is, when using R-1, during 1 '-union-2-naphthol, the solid product obtained by precipitation is S type diketone, and the product obtained by mother liquor is R type diketone, and use S-1, during 1 '-union-2-naphthol, the solid product obtained by precipitation is R type diketone, and the product obtained by mother liquor is S type diketone.
The series of experiments that the cited consumption on resolution solvent, fractionation time, temperature of reaction, chiral selectors and chiral selectors is done the impact of resolution yield and ee value by top embodiment, can conclude and draw following optimum condition: solvent is preferably toluene; Resolution reagent is R-1,1 '-union-2-naphthol or S-1, and 1 '-union-2-naphthol, the mol ratio of resolution reagent and chirality diketone is preferably 0.6:1; In temperature of reaction, be preferably 25 ℃ of reactions 6 hours; The volumetric molar concentration of chirality diketone is preferably 0.2mol/L.
Claims (5)
1. the method for a resolving chiral dione compounds, the mixed in molar ratio that elder generation presses 1:2:2 to methylene iodide, benzyl cyanide and Powdered sodium hydroxide is even, 145 ℃ the reaction 2 hours after, be cooled to room temperature, ratio according to every mole of methylene iodide adapted 125mL ether and 125mL water is diluted, then according to the ratio extracted with diethyl ether of every mole of methylene iodide adapted 250mL ether, the organic phase anhydrous sodium sulfate drying, filter, the benzyl cyanide that distillation is removed ether and do not reacted completely, obtain compound 2,4-phenylbenzene trimethylene cyanide, according to every gram 2, the ratio of the potassium hydroxide aqueous solution of 4-phenylbenzene trimethylene cyanide adapted 10mL ethanol and 10mL5mol/L is by 2, 4-phenylbenzene trimethylene cyanide mixes with ethanol and potassium hydroxide aqueous solution, after reflux 16 hours, cool to room temperature, ethanol is removed in distillation, by every gram 2, the ratio of 4-phenylbenzene trimethylene cyanide adapted 2mL ether is washed with ether, water is acidified to PH<7 with concentrated hydrochloric acid, by every gram 2, the ratio of 4-phenylbenzene trimethylene cyanide adapted 4mL ethyl acetate is extracted with ethyl acetate water, extraction obtains the organic phase anhydrous sodium sulfate drying, filter, ethyl acetate is removed in distillation, product is 2, 4-phenylbenzene pentanedioic acid, by every gram 2, the ratio of 4-phenylbenzene pentanedioic acid adapted vitriol oil 2mL is by 2,4-phenylbenzene pentanedioic acid and the vitriol oil mix, be heated to 85 ℃, react after 2 hours, by every gram 2, the ratio of 4-phenylbenzene pentanedioic acid adapted 10 gram ice, reaction solution is poured in ice, by every gram 2, the ratio of 4-phenylbenzene pentanedioic acid adapted toluene 6mL extracts with toluene, and organic phase alkalizes with saturated sodium bicarbonate aqueous solution, to PH>7, then use the saturated common salt water washing, anhydrous sodium sulfate drying, filter, toluene is removed in distillation, obtains structural formula and is
2,3:6,7-dibenzo dicyclo [3.3.1] is hot-2,6-diene-4,8-diketone, it is characterized in that: with structural formula, be
r-1,1'-union-2-naphthol or structural formula are
s-1, the 1'-union-2-naphthol to this 2,3:6,7-dibenzo dicyclo [3.3.1] hot-2,6-diene-4, the 8-diketone carries out chiral separation, presses mole proportioning of 0.5~1:1 by 1,1'-union-2-naphthol and 2,3:6,7-dibenzo dicyclo [3.3.1] suffering-2,6-diene-4, the 8-diketone mixes, take toluene or ethyl acetate as solvent, control 2,3:6,7-dibenzo dicyclo [3.3.1] hot-2,6-diene-4, the reaction density of 8-diketone is 0.1-0.33mol/L, mixes, 15-35 ℃ of reaction, after 1-24 hour, filter, the gained solid is mixed with toluene or the ethyl acetate solvent of equal volume again, the mixture obtained is washed by the aqueous sodium hydroxide washes of 1-5mol/L, after concentrated organic phase, obtain solid product, the employing ethyl acetate is recrystallization solvent, resulting solid product is carried out to recrystallization, obtain configuration that the ee value is higher with use 1, the dione compounds that 1'-union-2-naphthol configuration is contrary, again to the resulting mother liquor of aforementioned filtration, after washing by the aqueous sodium hydroxide washes of 1-5mol/L, concentrated organic phase, obtain solid product, the employing ethyl acetate is recrystallization solvent, the solid product obtained is carried out to recrystallization, obtain configuration that the ee value is higher with use 1, the dione compounds that 1'-union-2-naphthol configuration is identical.
2. the method for resolving chiral dione compounds as claimed in claim 1, be characterised in that described solvent adopts toluene.
3. the method for resolving chiral dione compounds as claimed in claim 1, be characterised in that described resolution reagent R-1,1 '-union-2-naphthol or S-1, and the mol ratio of 1 '-union-2-naphthol and chirality diketone is 0.6:1.
4. the method for resolving chiral dione compounds as claimed in claim 1, be characterised in that in temperature of reaction be 25 ℃, reacts 6 hours.
5. the method for resolving chiral dione compounds as claimed in claim 1, the volumetric molar concentration that is characterised in that described chirality diketone is 0.2mol/L.
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CN102627644A (en) * | 2012-04-10 | 2012-08-08 | 凯莱英医药集团(天津)股份有限公司 | Method for preparing sapropterin dihydrochloride through direct chiral synthesis method |
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CN112961037A (en) * | 2021-02-08 | 2021-06-15 | 浙江工业大学 | Method for resolving racemic chiral compound by molecular distillation method |
CN112961037B (en) * | 2021-02-08 | 2022-05-17 | 浙江工业大学 | Method for resolving racemic chiral compound by molecular distillation method |
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