CN101684071A - Method for splitting DL-p-hydroxymandelic acid - Google Patents
Method for splitting DL-p-hydroxymandelic acid Download PDFInfo
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Abstract
The invention relates to a method for splitting DL-p-hydroxymandelic acid racemate to prepare high purity D-p-hydroxymandelic acid. The method for splitting DL-p-hydroxymandelic acid is characterizedin that (S)-(+)-2-amino-4-phenylethyl butyrate hydrochloride is used as resolving agent to perform chemical splitting to DL-p-hydroxymandelic acid. The method of the invention solves the problems of too many operation steps, long reaction time, low product purity, low yield and the like in the existing method for preparing high purity D-p-hydroxymandelic acid by splitting DL-p-hydroxymandelic acidracemate.
Description
Technical field
The present invention relates to a kind of DL-of fractionation parahydroxymandelic acid racemic modification and produce the method for high purity D-parahydroxymandelic acid.
Background technology
The DL-parahydroxymandelic acid is the intermediate of important medicine, agricultural chemicals and spices, especially at the intermediate that pharmaceutically is being preparation antihypertensive agent atenolol USP 23 (Atenolol), also is the intermediate of preparation spectrum antibiotic new drug amoxycilline Trihydrate bp.But the parahydroxymandelic acid that method economy, common usually synthesizes is not have chirality, has special purposes and exactly have optically active parahydroxymandelic acid on medicine or biomedicine field.Can be used for the synthetic sweet acid of left-handed para hydroxybenzene as the D-parahydroxymandelic acid, and then synthetic Broad spectrum antibiotics amoxycillin and amoxycillin cephalo, cefoperazone, cephalo Luo Qi and SKF-60771 etc., simultaneously, D-parahydroxymandelic acid and derivative thereof have broad application prospects in field such as antimicrobial, antiviral.
At present, not finding the bibliographical information that the DL-parahydroxymandelic acid splits, below is the method for several fractionation DL-amygdalic acids:
1, with chirality phenylalanine, D-phenylglycine butyl ester as resolving agent
Ryoichi etc. are with racemic amygdalic acid and optically active phenylalanine is water-soluble or other solvent, in order to increase the solubleness of initiator, must add number acid in solvent.After mixture is warming up to 70～72 ℃, slowly cool to 35 ℃, obtain L-(+)-amygdalic acid L-(-)-phenylalanine mixture crystal of 1: 1, obtain optical purity after handling with NaOH and be L-(+)-amygdalic acid of 98.4%, from filtrate, separate having obtained D-(-)-amygdalic acid.Owing in resolution solvent, added acid solution, increased the intractability of follow-up extraction.
U.S. Pat 4322548 has used D-phenylglycine butyl ester as resolving agent, concrete operations are as follows: D-phenylglycine butyl ester (or its hydrochloride) and DL-amygdalic acid reaction back suction filtration crystallisate, usage quantity according to HCl neutralizes with alkali, and temperature of reaction is between 0～35 ℃.Extract with the amygdalic acid after the fractionation of handles such as water-immiscible solvent such as methyl tertiary butyl ether, ether.
2, with D-(-)-2-amino-1-butanols as resolving agent
It is the process that resolving agent splits racemic mandelic acid that U.S. Pat 4259521 is described in detail with optically active 2-amino-1-butanols, and has done corresponding improvement.Split process comprises: the 2-amino-1-butanols of optically-active amygdalic acid of (or low-carbon alcohol or their mixture) and racemization in water reacts between 20～60 ℃, forms the mandelate salt of optically-active; Cooled reaction solution, Crystallization Separation go out the mandelate salt of optically-active; Isolated mandelate salt is soluble in water, distills out any residual alcohols between 50 ℃ to 90 ℃; With inorganic acid for adjusting pH is 0.5～1.2, to produce the amygdalic acid of optically-active; Cooling reactant-5 ℃～5 ℃ obtains the amygdalic acid of optically-active.Whole yields of last D-(-) or L-(+) amygdalic acid are 75%～85% of theoretical yield, and used water is carried out recrystallization and improved purity.
3, biological fermentation splits
Japanese Patent JP57198097 has reported with the benzoyl formic acid to be substrate, with lactobacillus or Pediococcus 30 ℃ of bottom fermentations 24 hours, behind ethyl acetate extraction, with normal hexane and acetone (V/V, 3/1) mixed solvent is purified on silicagel column, obtains colourless crystallisate L-(+)-amygdalic acid at last.Owing to consumed the raw material of half, so yield is lower.
More above-mentioned several technology exists operation steps many, long reaction time, and problem such as product purity is not high, and yield is low, little for the reference that the DL-parahydroxymandelic acid splits.
Summary of the invention
Technical problem to be solved by this invention is to propose a kind of method of the DL-of fractionation parahydroxymandelic acid, to reach the purpose of producing high purity D-parahydroxymandelic acid from DL-parahydroxymandelic acid racemic modification, this method steps is simple, easy handling, reaction times is short, product purity can reach more than 99%, is suitable for need of industrial production.
The present invention solves the problems of the technologies described above by the following technical solutions, reaches purpose of the present invention.
A kind of method that splits the DL-parahydroxymandelic acid, this method are used (S)-(+)-2-amino-4-phenylbutyrate hydrochloride as resolving agent the DL-parahydroxymandelic acid to be carried out chemistry and are split.
(S)-(+)-2-amino-4-phenylbutyrate hydrochloride and DL-parahydroxymandelic acid are reacted the reaction product that obtains diastereomer, there is significant difference in the solvability of the reaction product of both diastereomers in some solvent, utilize this difference that the reaction product of both diastereomers is split, and then produce out highly purified D-parahydroxymandelic acid.
According to top technical scheme, further design following technical scheme and from DL-parahydroxymandelic acid racemic modification, produce high purity D-parahydroxymandelic acid.
A kind of method that splits the DL-parahydroxymandelic acid may further comprise the steps:
1) under the protection and stirring of shielding gas, drop into (S)-(+)-2-amino-4-phenylbutyrate hydrochloride and the DL-parahydroxymandelic acid of reacting weight in the reaction medium in reactor, react, form reaction solution;
2) with the cooling of the reaction solution in the reactor of described step 1), in described reactor, add alkali, produce D-parahydroxymandelic acid double salt (D-parahydroxymandelic acid double salt is D-parahydroxymandelic acid (S)-(+)-2-amino-4-phenylbutyrate) precipitation;
3) with described step 2) reactor in reacting liquid filtering, dry D-parahydroxymandelic acid double salt precipitation obtains filtrate A and D-parahydroxymandelic acid double salt;
4) add the acid of reacting weight in the D-parahydroxymandelic acid double salt that in described step 3), obtains, react, form reaction solution;
5) with the reaction solution organic solvent extraction of described step 4), obtain organic phase and aqueous phase B;
6) organic solvent of the organic phase that obtains in the described step 5) is sloughed, obtained D-parahydroxymandelic acid crude product;
7) with the D-parahydroxymandelic acid crude product washing that obtains in the described step 6), after vacuum-drying, get the D-parahydroxymandelic acid.
Preferably, in the described step 1), described shielding gas is a nitrogen.
Preferably, in the described step 1), the mol ratio of (S)-(+) that drops in the reaction medium in described reactor-2-amino-4-phenylbutyrate hydrochloride and DL-parahydroxymandelic acid is 1: 1.
Preferably, in the described step 1), reaction medium is the mixed solvent of water, lower aliphatic alcohols, and mass percent concentration is 20～50%; Temperature of reaction is 50 ℃～80 ℃; Reaction times is 15～100min.Further, described lower aliphatic alcohols is a kind of in ethanol, n-propyl alcohol, the Virahol.
Preferably, described step 2) in, also comprise the step of the cooling of the reaction solution in the reactor of described step 1), be cooled to 10 ℃.Can fully separate out D-parahydroxymandelic acid double salt like this, improve yield.
Preferably, described step 2) in, the alkali that adds in described reactor is NaOH or KOH.
Preferably, in the described step 4), the acid of the reacting weight that adds in the D-parahydroxymandelic acid double salt that obtains in described step 3) is dilute hydrochloric acid, and the molar ratio of D-parahydroxymandelic acid double salt and HCl is 1: 1～1: 1.5, temperature of reaction is controlled at 20～45 ℃, and the reaction times is 30～60min.
Preferably, in the described step 5), the reaction solution with described step 4) is cooled to 5～10 ℃ earlier, extracts with ether, sherwood oil or DMF then.
Preferably, in the described step 7), adopt methyl alcohol, ethanol or propyl alcohol that described D-parahydroxymandelic acid crude product is washed.
Preferably, the present invention uses 4-nitro-phenyl aldehyde as catalyzer.
The present invention has also solved the recovery problem of filtrate A, (S)-(+)-2-amino-4-phenylbutyrate hydrochloride.
The recycling step of filtrate A is as follows: with the filtrate A in the described step 3), regulate pH value to 6～7, add an amount of 4-nitro-phenyl aldehyde, be warming up to 85～95 ℃, keep 30min, obtain splitting mother liquor D.Split mother liquor D can directly split usefulness as next batch mother liquor D.
(S)-(+)-and the recycling step of 2-amino-4-phenylbutyrate hydrochloride is as follows: the aqueous phase B in the described step 5) is removed most water through underpressure distillation, obtain bottoms, described bottoms obtains solid C after filtering, with described solid C under 90～100 ℃ of conditions, cure, at least 2 hours time, obtain solid (S)-(+)-2-amino-4-phenylbutyrate hydrochloride.Solid (S)-(+)-2-amino-4-phenylbutyrate hydrochloride that reclaims, can be directly as the resolving agent of next batch.
As a kind of method for splitting of DL-parahydroxymandelic acid, the present invention is the method that a kind of not only economically feasible but also the suitable industrialization with efficient fractionation efficient are amplified.As the technology that splits the DL-parahydroxymandelic acid, the present invention has the following advantages and effect:
1. use cheap solvent, and be easy to reclaim,, reduced the usage quantity of solvent, reduced production cost by splitting recycling of mother liquor.
2. adopt resolving agent (S)-(+)-2-amino-4-phenylbutyrate and catalyzer 4-nitro-phenyl aldehyde that reaction yield is improved greatly.
3. successfully utilize the characteristic of the resolving agent that uses, solved the too much problem of resolving agent loss in the split process, and well carried out recovery set usefulness.
Description of drawings
Fig. 1 is to use (S)-(+)-2-amino-4-phenylbutyrate hydrochloride as catalyzer the DL-parahydroxymandelic acid to be carried out the route map that chemistry splits as resolving agent, 4-nitro-phenyl aldehyde.
Fig. 2 is the schema that splits the method for DL-parahydroxymandelic acid in the embodiment.
Embodiment
Further specify technical scheme of the present invention below in conjunction with accompanying drawing.
The DL-parahydroxymandelic acid raw material that adopts in the embodiment, chemical purity is greater than 98%.
Referring to Fig. 1, Fig. 2.The method of fractionation DL-parahydroxymandelic acid of the present invention; be with (S)-(+)-2-amino-4-phenylbutyrate hydrochloride the DL-parahydroxymandelic acid to be carried out chemistry to split; specifically; be in nitrogen protection; under the condition of continuously stirring; (S)-(+)-2-amino-4-phenylbutyrate hydrochloride and the DL-parahydroxymandelic acid that will react mol ratio and be 1: 1 join in the reactor; reaction medium in the reactor is a water; the mixed solvent of lower aliphatic alcohols; mass percent concentration is 20～50%; 50 ℃～80 ℃ of control reaction temperature; reaction times is 15～100min; be cooled to 10 ℃ then; slowly drip NaOH solution, produce white precipitate, then filter; drying gets filtrate A and D-parahydroxymandelic acid double salt.
Add dilute hydrochloric acid solution in D-parahydroxymandelic acid double salt, the molar ratio of control D-parahydroxymandelic acid double salt and hydrochloric acid is 1: 1～1: 1.5, and temperature of reaction is controlled at 20～45 ℃, and the reaction times is 30～60min.Reaction is cooled to 5～10 ℃ after finishing, and adds ether and extracts, and obtains organic phase and aqueous phase B.Aqueous phase B is recycled, and organic phase simple distillation obtains light yellow solid after sloughing solvent ether, is D-parahydroxymandelic acid crude product.This D-parahydroxymandelic acid crude product washs with small amount of ethanol, gets the D-parahydroxymandelic acid after vacuum-drying.
Filtrate A adds an amount of 4-nitro-phenyl aldehyde after regulating pH value to 6～7, be warming up to 85～95 ℃, keeps 30min.Under 4-nitro-phenyl aldehyde catalysis, L-parahydroxymandelic acid double salt among the filtrate A and D-parahydroxymandelic acid double salt transform mutually, filtrate A can be directly as the fractionation mother liquor D of next batch.
Aqueous phase B is through underpressure distillation, obtains bottoms after removing most of moisture, and bottoms can get solid C after filtering.Under 90～100 ℃ of conditions, place Ma Fulu or baking oven to cure solid C, 2 hours time, reclaim solid (S)-(+)-2-amino-4-phenylbutyrate hydrochloride, can directly be used as the resolving agent of next batch.
Embodiment 1
Get DL-parahydroxymandelic acid 8.4 grams (0.05mol), (S)-(+)-2-amino-4-phenylbutyrate hydrochloride 12.18 grams (0.05mol), put in the aqueous ethanolic solution of 120ml 30%, open stirring, N
2Protection is warming up to 75 ℃, forms transparent reaction solution, slowly adds 2 gram (0.05mol) sodium hydroxide subsequently, and after the continuation stirring reaction carried out 30min, the adularescent precipitation produced, and slowly is cooled to 10 ℃, allowed the D-parahydroxymandelic acid double salt that forms fully separate out.Filtration under diminished pressure obtains filtrate A and 9.07 gram white crystals, yield is 97% of a theoretical yield, this white crystal is D-parahydroxymandelic acid double salt (D-parahydroxymandelic acid (S)-(+)-2-amino-4-phenylbutyrate), after the small amount of ethanol washing, places vacuum drying oven dry.
Take by weighing dried D-parahydroxymandelic acid (S)-(+)-2-amino-4-phenylbutyrate 9.07 grams, be dissolved in the 46g mass percent concentration and be in 2% the dilute hydrochloric acid solution, open and stir, the molar ratio of D-parahydroxymandelic acid double salt and hydrochloric acid is 1: 1, temperature of reaction is controlled at 30 ℃, and the reaction times is 40min.Reaction is cooled to 10 ℃ after finishing, and adds ether and extracts, and obtains organic phase and aqueous phase B.Aqueous phase B is recycled, and organic phase obtains light yellow solid after sloughing solvent ether, is D-parahydroxymandelic acid crude product.This light yellow solid is washed with small amount of ethanol, after vacuum-drying, weigh to such an extent that D-parahydroxymandelic acid 3.9 restrains yield 95.1%.The D-parahydroxymandelic acid after testing,
Chemical purity is greater than 99%.
Add 1g 4-nitro-phenyl aldehyde to filtrate A, be warming up to 85 ℃, reduce to room temperature behind the stirring reaction 30min, this filtrate can be directly as the fractionation mother liquor D of next batch.
Aqueous phase B is after underpressure distillation boils off most of water, cool to normal temperature, filter, can obtain the white mixture of resolving agent (S)-(+)-2-amino-4-phenylbutyrate hydrochloride, at 90～100 ℃, white mixture places baking oven to cure, 2 hours time, reclaim solid (S)-(+)-2-amino-4-phenylbutyrate hydrochloride, can directly be used as the resolving agent of next batch.
Embodiment 2
Get (S)-(+)-2-amino-4-phenylbutyrate hydrochloride 12.18 grams (0.05mol), put into the 120ml mass percent concentration and be in 50% the aqueous ethanolic solution, open stir, N
2Protection is warming up to 55 ℃, slowly adds 2 gram (0.05mol) sodium hydroxide subsequently, forms transparent reaction solution.Add DL-parahydroxymandelic acid 8.4 grams (0.05mol) subsequently, after the continuation stirring reaction carried out 80min, the adularescent precipitation produced, and slowly is cooled to 10 ℃, allowed the D-parahydroxymandelic acid double salt that forms fully separate out.Resultant white crystal 9.18 gram and the filtrate A of filtration under diminished pressure, yield is 98.2% of a theoretical yield, this white crystal is D-parahydroxymandelic acid (S)-(+)-2-amino-4-phenylbutyrate, after the small amount of ethanol washing, places vacuum drying oven dry.
Take by weighing dried D-parahydroxymandelic acid (S)-(+)-2-amino-4-phenylbutyrate 9.18 grams, be dissolved in the 55g mass percent concentration and be in 2% the dilute hydrochloric acid solution, open and stir, the molar ratio of D-parahydroxymandelic acid double salt and hydrochloric acid is 1: 1.2, temperature of reaction is controlled at 40 ℃, and the reaction times is 60min.Reaction is cooled to 5 ℃ after finishing, and adds ether and extracts, and aqueous phase B is recycled, and organic phase obtains light yellow solid after sloughing solvent ether, is D-parahydroxymandelic acid crude product.This light yellow solid washs with small amount of ethanol, weighs to such an extent that D-parahydroxymandelic acid 4.0 restrains theoretical yield 97.5% after vacuum-drying.The D-parahydroxymandelic acid through the check,
Chemical purity is greater than 99%.
Filtrate A adds 4-nitro-phenyl aldehyde adding an amount of second acid for adjusting pH value to 6～7, is warming up to 90 ℃, keeps 30min, can be directly as the fractionation mother liquor D of next batch.
Aqueous phase B is after underpressure distillation boils off most of water, cool to normal temperature, filter, can obtain the white mixture of resolving agent (S)-(+)-2-amino-4-phenylbutyrate hydrochloride, at 90～100 ℃, white mixture places baking oven to cure, 2 hours time, reclaim solid (S)-(+)-2-amino-4-phenylbutyrate hydrochloride, can directly be used as the resolving agent of next batch.
Embodiment 3
(S)-(+)-2-amino-4-phenylbutyrate hydrochloride 12.2 grams and DL-parahydroxymandelic acid 8.4 grams that take by weighing recovery mix, and other conditions are with embodiment 1.Make D-parahydroxymandelic acid 3.75 grams at last, theoretical yield 93.3%.The D-parahydroxymandelic acid through the check,
Chemical purity is greater than 98%.
Embodiment 4
Utilize the fractionation mother liquid filtrate D among the embodiment 1, add DL-parahydroxymandelic acid 4.2g (0.025mol) and (S)-(+)-2-amino-4-phenylbutyrate hydrochloride 6.1 grams (0.025mol), open stirring, nitrogen protection, be warming up to 80 ℃.Other conditions are with embodiment 2.Make D-parahydroxymandelic acid 3.85 grams at last, theoretical yield reaches 95.8%.The D-parahydroxymandelic acid through the check,
Chemical purity is greater than 98%.
Those of ordinary skill in the art will be appreciated that, above embodiment is used for illustrating the present invention, and be not to be used as limitation of the invention, as long as in connotation scope of the present invention, all will drop in claims scope of the present invention variation, the modification of the above embodiment.
Claims (14)
1, a kind of method that splits the DL-parahydroxymandelic acid is characterized in that, this method is used (S)-(+)-2-amino-4-phenylbutyrate hydrochloride as resolving agent the DL-parahydroxymandelic acid to be carried out chemistry and split.
2, a kind of method that splits the DL-parahydroxymandelic acid according to claim 1 is characterized in that, may further comprise the steps:
1) under the protection and stirring of shielding gas, drop into (S)-(+)-2-amino-4-phenylbutyrate hydrochloride and the DL-parahydroxymandelic acid of reacting weight in the reaction medium in reactor, react, form reaction solution;
2) add alkali in the reaction solution in the reactor of described step 1), produce D-parahydroxymandelic acid double salt precipitation;
3) with described step 2) reactor in reacting liquid filtering, dry D-parahydroxymandelic acid double salt precipitation obtains filtrate A and D-parahydroxymandelic acid double salt;
4) add the acid of reacting weight in the D-parahydroxymandelic acid double salt that in described step 3), obtains, react, form reaction solution;
5) with the reaction solution organic solvent extraction of described step 4), obtain organic phase and aqueous phase B;
6) organic solvent of the organic phase that obtains in the described step 5) is sloughed, obtained D-parahydroxymandelic acid crude product;
7) with the D-parahydroxymandelic acid crude product washing that obtains in the described step 6), after vacuum-drying, get the D-parahydroxymandelic acid.
3, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2 is characterized in that: in the described step 1), described shielding gas is a nitrogen.
4, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2, it is characterized in that: in the described step 1), the mol ratio of (S)-(+) that drops in the reaction medium in described reactor-2-amino-4-phenylbutyrate hydrochloride and DL-parahydroxymandelic acid is 1: 1.
5, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2 is characterized in that: in the described step 1), reaction medium is the mixed solvent of water, lower aliphatic alcohols, and mass percent concentration is 20～50%; Temperature of reaction is 50 ℃～80 ℃; Reaction times is 15～100min.
6, a kind of method that splits the DL-parahydroxymandelic acid according to claim 5 is characterized in that: described lower aliphatic alcohols is a kind of in ethanol, n-propyl alcohol, the Virahol.
7, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2 is characterized in that: described step 2), also comprise the step of the cooling of the reaction solution in the reactor of described step 1), be cooled to 5～10 ℃.
8, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2 is characterized in that: described step 2), the alkali that adds in described reactor can be NaOH or KOH.
9, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2, it is characterized in that: in the described step 4), the acid of the reacting weight that adds in the D-parahydroxymandelic acid double salt that obtains in described step 3) is dilute hydrochloric acid, the molar ratio of D-parahydroxymandelic acid double salt and HCl is 1: 1～1: 1.5, temperature of reaction is controlled at 20～45 ℃, and the reaction times is 30～60min.
10, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2 is characterized in that: in the described step 5), the reaction solution with described step 4) is cooled to 5～10 ℃ earlier, extracts with ether, sherwood oil or DMF then.
11, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2 is characterized in that: in the described step 7), adopt methyl alcohol, ethanol or propyl alcohol that described D-parahydroxymandelic acid crude product is washed.
12, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2, it is characterized in that: the recycling step that also comprises filtrate A, this step is with the filtrate A in the described step 3), regulate pH value to 6～7, add an amount of 4-nitro-phenyl aldehyde, be warming up to 85～95 ℃, keep 30min, obtain splitting mother liquor D.
13, a kind of method that splits the DL-parahydroxymandelic acid according to claim 2, it is characterized in that: the recycling step that also comprises (S)-(+)-2-amino-4-phenylbutyrate hydrochloride, this step is removed most of water with the aqueous phase B in the described step 5) through underpressure distillation, obtain bottoms, described bottoms obtains solid C after filtering, with described solid C under 90～100 ℃ of conditions, cure, at least 2 hours time, obtain solid (S)-(+)-2-amino-4-phenylbutyrate hydrochloride.
14, a kind of method that splits the DL-parahydroxymandelic acid according to claim 1 and 2 is characterized in that: use 4-nitro-phenyl aldehyde as catalyzer.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102126944A (en) * | 2010-12-15 | 2011-07-20 | 郑州大学 | Method for preparing single configuration mandelic acid or mandelic acid derivative by using chiral resolving agent |
| CN102603518A (en) * | 2012-01-30 | 2012-07-25 | 郑州大学 | Resolution method for 2-chloromandelic acid by crystalizing diastereomeric salts |
| CN109467502A (en) * | 2018-11-21 | 2019-03-15 | 湖南科技大学 | A method of splitting almond acid compounds enantiomer |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100372926C (en) * | 2005-06-23 | 2008-03-05 | 华东理工大学 | Pseudomonas putida and application thereof for mandelic acid racemate resolution |
| CN101134943B (en) * | 2007-05-11 | 2010-05-19 | 华东理工大学 | Bacillus alcaligenes and method for preparing single enantiomer amygdalic acid |
| CN101417942B (en) * | 2007-10-26 | 2011-09-21 | 宝山钢铁股份有限公司 | Method for preparing p-hydroxymandelic acid |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102126944A (en) * | 2010-12-15 | 2011-07-20 | 郑州大学 | Method for preparing single configuration mandelic acid or mandelic acid derivative by using chiral resolving agent |
| CN102126944B (en) * | 2010-12-15 | 2013-12-18 | 郑州大学 | Method for preparing single configuration mandelic acid or mandelic acid derivative by using chiral resolving agent |
| CN102603518A (en) * | 2012-01-30 | 2012-07-25 | 郑州大学 | Resolution method for 2-chloromandelic acid by crystalizing diastereomeric salts |
| CN109467502A (en) * | 2018-11-21 | 2019-03-15 | 湖南科技大学 | A method of splitting almond acid compounds enantiomer |
| CN109467502B (en) * | 2018-11-21 | 2021-07-30 | 湖南科技大学 | Method for splitting mandelic acid compound enantiomer |
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