CN102516034A - Chiral resolution method of racemic 1,1'-bi-2-naphthol - Google Patents
Chiral resolution method of racemic 1,1'-bi-2-naphthol Download PDFInfo
- Publication number
- CN102516034A CN102516034A CN2011104164740A CN201110416474A CN102516034A CN 102516034 A CN102516034 A CN 102516034A CN 2011104164740 A CN2011104164740 A CN 2011104164740A CN 201110416474 A CN201110416474 A CN 201110416474A CN 102516034 A CN102516034 A CN 102516034A
- Authority
- CN
- China
- Prior art keywords
- naphthol
- union
- racemization
- chiral
- inclusion complex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- PPTXVXKCQZKFBN-UHFFFAOYSA-N Oc(ccc1c2cccc1)c2-c1c(cccc2)c2ccc1O Chemical compound Oc(ccc1c2cccc1)c2-c1c(cccc2)c2ccc1O PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 description 1
Images
Abstract
The invention discloses a chiral resolution method of racemic 1,1'-bi-2-naphthol, relating to the racemic 1,1'-bi-2-naphthol. The method comprises the following steps: adding a solvent in the racemic 1,1'-bi-2-naphthol and chiral quaternary ammonium salt, stirring, carrying out suction filtration and separating the solid phase and liquid phase of a suspension, respectively collecting an indissolvable inclusion complex solution and a soluble inclusion complex solution, and carrying out air drying; dissolving the air-dried indissolvable inclusion complexes and soluble inclusion complexes in a mixed solvent, carrying out liquid separation, respectively collecting a two-phase solution, carrying out air drying, respectively collecting obtained solids from the ether phase of the indissolvable inclusion complexes and the soluble inclusion complexes and using the collected solids as a pair of crude products of chiral 1,1-bi-2-naphthol with opposite chirality, recovering solids from the water phase and using the recovered solids as resolving agent chiral quaternary ammonium salts; carrying out recrystallization on the crude products of chiral 1,1-bi-2-naphthol to obtain a pair of chiral 1,1-bi-2-naphthol with opposite chirality, wherein the chiral quaternary ammonium salts synthesized by replacing CH3Br which has the characteristics of volatility and severe pollution by CH3I are used as the resolving agent.
Description
Technical field
The present invention relates to racemization 1,1 '-union-2-naphthol, especially relate to a kind of racemization 1,1 '-chiral separation method of union-2-naphthol.
Background technology
The inclusion Split Method is to be invented by Japanization scholar professor Toda the eighties in 20th century.The chirality host compound is through hydrogen bond and intermolecular noncovalent interaction, like π-π effect etc., optionally with guest molecule in enantiomer form stable super molecular compound (inclusion complex compound, abbreviation inclusion complex).Through dissociating of indissoluble inclusion complex, can realize Separation of Enantiomers (Feng Xiaoming, etc. organic chemistry, 2000,20 (2): 131-137).2 hydroxy functional groups of BINOL have good reactive behavior, can be reacted into ester or become ether with chiral reagent, obtain diastereomer, utilize its nature difference to split, and are purified at last, dissociate, and obtain the mapping pure products.The chemical method for splitting of existing many racemize BINOL mainly comprises into the ester method, becomes ether method, complexing crystallization process etc. so far.But these methods all exist synthetic loaded down with trivial details, the resolving agent expensive raw materials of resolving agent, raw material and solvent unfriendly to environment to some extent, diastereomer or inclusion complex shortcoming such as be difficult to dissociate, and be not suitable for the pilot scale that fine chemistry industry produces and amplify.Toda etc. are raw material with inexpensive natural amino acid, synthetic quaternary ammonium salt resolving agent, utilize the inclusion method successfully split 1,1 '-union-2-naphthol (Toda F, Tanaka K.Chem.Commun., 1997,12 (10): 1087-1088).
Summary of the invention
The object of the invention aims to provide a kind of green high-efficient, with CH
3I replaces highly volatile and seriously polluted CH
3Br synthetic chiral quaternary ammonium salt be resolving agent racemization 1,1 '-chiral separation method of union-2-naphthol.
Concrete fractionation route of the present invention is following:
Wherein, R
1, R
2Inequality, R
1, R
2Represent sec.-butyl or methylol respectively; Subscript+,-1 positive electricity, 1 negative electricity are with in the representative representative respectively; BINOL represents 1,1 '-union-2-naphthol; Ether represents ether; It is R that R represents the absolute configuration of its this chipal compounds; It is S that S represents the absolute configuration of its this chipal compounds.
Its concrete splitting step is following:
1) toward racemization 1,1 '-add solvent in union-2-naphthol and the chiral quaternary ammonium salt, stirring, the liquid-solid liquid phase of suction filtration separate out suspended is collected indissoluble inclusion complex and Yi Rong inclusion complex solution respectively, and is air-dry;
2) air-dry back indissoluble inclusion complex and the easy inclusion complex that dissolves are dissolved in mixed solvent respectively; Separatory is collected two phase liquid respectively, and is air-dry; Collect the solid that obtains mutually respectively from indissoluble inclusion complex and the easy inclusion complex ether that dissolves; For a pair of chirality 1,1 of opposite chirality '-the union-2-naphthol crude product, and the solid that reclaims from water is the resolving agent chiral quaternary ammonium salt;
3) to 1,1 '-the union-2-naphthol crude product carries out recrystallization, promptly obtain a pair of chirality 1,1 of opposite chirality '-union-2-naphthol, its e.e value can reach 99.99%.
In step 1), said racemization 1,1 '-union-2-naphthol and chiral quaternary ammonium salt can be 2: 1 in molar ratio; Said solvent can be ethanol etc.; Said racemization 1,1 '-ratio of union-2-naphthol and quantity of solvent can be 1.19g: 6mL; The time of said stirring can be 24～72h, and the temperature of said stirring can be 0～30 ℃.
In step 2) in, said mixed solvent can be the ether water mixed liquid, and the volume ratio of said ether and water can be 1: (0.5～2).
In step 3), said to 1,1 '-the union-2-naphthol crude product carries out recrystallization, available ether to 1,1 '-the union-2-naphthol crude product carries out recrystallization at least 1 time.
The present invention provide 1,1 of a kind of green high-efficient '-the union-2-naphthol chiral separation method, be resolving agent with the chiral quaternary ammonium salt, adopt the inclusion method split racemization 1,1 '-union-2-naphthol, can get the pure dinaphthol of mapping.The chemical method for splitting of existing many racemize BINOL all is not suitable for the pilot scale amplification that fine chemistry industry is produced so far.Present method is simple to operate, productive rate is high, environmental protection, and resolving agent is easy to reclaim, and has fabulous industrial prospect.
Description of drawings
Fig. 1 is that the HPLC of indissoluble inclusion complex (calling inclusion complex 1 in the following text) analyzes.In Fig. 1, X-coordinate is time t/min, and ordinate zou is voltage U/mv; The structural formula of said inclusion complex 1 is:
Fig. 2 is that the HPLC of indissoluble inclusion complex (calling inclusion complex 2 in the following text) analyzes.In Fig. 2, X-coordinate is time t/min, and ordinate zou is voltage U/mv; The structural formula of said inclusion complex 2 is:
Fig. 3 analyzes for the HPLC of racemization BINOL.In Fig. 3, X-coordinate is time t/min, and ordinate zou is voltage U/mv.
Embodiment
Following examples are described further the present invention.
Embodiment 1
(1.19g, 4.16mmol) (0 ℃ of lower magnetic force stirs 72h, the separating obtained solid-liquid suspension phase of suction filtration for 0.597g, 2.08mmol) the middle 6mL absolute ethyl alcohol that adds with L-Isoleucine deutero-chiral quaternary ammonium salt toward racemization BINOL.Analyze through chirality HPLC, white powder is the indissoluble inclusion complex (84.0%e.e.) of S-BINOL and this chiral quaternary ammonium salt, filtrates to comprising the molten inclusion complex solution that is prone to of R-BINOL (45.0%e.e.) and this chiral quaternary ammonium salt.Air-dry back indissoluble inclusion complex and Yi Rong inclusion complex solution are dissolved in respectively in ether water (1: the 2) mixed solution, and separatory is collected two phase liquid respectively, and is air-dry.Collect the solid that obtains mutually from ether and be chirality BINOL crude product, and the solid that reclaims from water is this chiral quaternary ammonium salt.Through with ether the BINOL crude product being carried out repeatedly product S-BINOL 0.41g, the R-BINOL 0.31g that recrystallization can obtain e.e value 99.99%, productive rate is respectively 68.9%, 52.1%.
(1.19g, 4.16mmol) (30 ℃ of lower magnetic forces stir 24h, the separating obtained solid-liquid suspension phase of suction filtration for 0.597g, 2.08mmol) the middle 6mL absolute ethyl alcohol that adds with D-Isoleucine deutero-chiral quaternary ammonium salt toward racemization BINOL.Analyze through chirality HPLC, white powder is the indissoluble inclusion complex (78.7%e.e.) of R-BINOL and this chiral quaternary ammonium salt, filtrates to comprising the molten inclusion complex solution that is prone to of S-BINOL (48.3%e.e.) and this chiral quaternary ammonium salt.Air-dry back indissoluble inclusion complex and Yi Rong inclusion complex solution are dissolved in respectively in ether water (1: the 1) mixed solution, and separatory is collected two phase liquid respectively, and is air-dry.Collect the solid that obtains mutually from ether and be chirality BINOL crude product, and the solid that reclaims from water is this chiral quaternary ammonium salt.Through with ether the BINOL crude product being carried out repeatedly product S-BINOL 0.38g, the R-BINOL 0.35g that recrystallization can obtain e.e value 99.99%, productive rate is respectively 63.9%, 58.9%.
Embodiment 3
(1.19g is 4.16mmol) with L-Isoleucine deutero-chiral quaternary ammonium salt (0.597g, 2.08mmol) middle 6mL absolute ethyl alcohol, 15 ℃ of magnetic agitation 48h, the separating obtained solid-liquid suspension phase of suction filtration of adding toward racemization BINOL.Analyze through chirality HPLC, white powder is the indissoluble inclusion complex (79.6%e.e.) of S-BINOL and this chiral quaternary ammonium salt, filtrates to comprising the molten inclusion complex solution that is prone to of R-BINOL (49.5%e.e.) and this chiral quaternary ammonium salt.Air-dry back indissoluble inclusion complex and Yi Rong inclusion complex solution are dissolved in respectively in ether water (1: the 0.5) mixed solution, and separatory is collected two phase liquid respectively, and is air-dry.Collect the solid that obtains mutually from ether and be chirality BINOL crude product, and the solid that reclaims from water is this chiral quaternary ammonium salt.Through with ether the BINOL crude product being carried out repeatedly product S-BINOL 0.43g, the R-BINOL 0.30g that recrystallization can obtain e.e value 99.99%, productive rate is respectively 72.3%, 504%.
Inclusion complex 1, inclusion complex 2 and the racemization BINOL that obtains in the split process carried out HPLC analyze the experimental result that can obtain Fig. 1～Fig. 3.Wherein Fig. 1 is the HPLC analysis of inclusion complex 1, and Fig. 2 is that the HPLC of inclusion complex 2 analyzes, and Fig. 3 analyzes for the HPLC of racemization BINOL.
Claims (9)
1. racemization 1 '-chiral separation method of union-2-naphthol, it is characterized in that it, concrete to split route following:
Wherein, R
1, R
2Inequality, R
1, R
2Represent sec.-butyl or methylol respectively; Subscript+,-1 positive electricity, 1 negative electricity are with in the representative representative respectively; BINOL represents 1,1 '-union-2-naphthol; Ether represents ether; It is R that R represents the absolute configuration of its this chipal compounds; It is S that S represents the absolute configuration of its this chipal compounds.
2. racemization 1,1 as claimed in claim 1 '-chiral separation method of union-2-naphthol, it is characterized in that its concrete splitting step is following:
1) toward racemization 1,1 '-add solvent in union-2-naphthol and the chiral quaternary ammonium salt, stirring, the liquid-solid liquid phase of suction filtration separate out suspended is collected indissoluble inclusion complex and Yi Rong inclusion complex solution respectively, and is air-dry;
2) air-dry back indissoluble inclusion complex and the easy inclusion complex that dissolves are dissolved in mixed solvent respectively; Separatory is collected two phase liquid respectively, and is air-dry; Collect the solid that obtains mutually respectively from indissoluble inclusion complex and the easy inclusion complex ether that dissolves; For a pair of chirality 1,1 of opposite chirality '-the union-2-naphthol crude product, and the solid that reclaims from water is the resolving agent chiral quaternary ammonium salt;
3) to 1,1 '-the union-2-naphthol crude product carries out recrystallization, promptly obtain a pair of chirality 1,1 of opposite chirality '-union-2-naphthol, its e.e value can reach 99.99%.
3. racemization 1,1 as claimed in claim 2 '-chiral separation method of union-2-naphthol, it is characterized in that in step 1), said racemization 1,1 '-union-2-naphthol and chiral quaternary ammonium salt are 2: 1 in molar ratio.
4. racemization 1,1 as claimed in claim 2 '-chiral separation method of union-2-naphthol, it is characterized in that in step 1) said solvent is an ethanol.
5. racemization 1,1 as claimed in claim 2 '-chiral separation method of union-2-naphthol, it is characterized in that in step 1), said racemization 1,1 '-ratio of union-2-naphthol and quantity of solvent is 1.19g: 6mL.
6. racemization 1,1 as claimed in claim 2 '-chiral separation method of union-2-naphthol, it is characterized in that in step 1) the time of said stirring is 24～72h, the temperature of said stirring is 0～30 ℃.
7. racemization 1,1 as claimed in claim 2 '-chiral separation method of union-2-naphthol, it is characterized in that in step 2) in, said mixed solvent is the ether water mixed liquid.
8. racemization 1,1 as claimed in claim 2 '-chiral separation method of union-2-naphthol, it is characterized in that in step 2) in, the volume ratio of said ether and water is 1: (0.5～2).
9. racemization 1,1 as claimed in claim 2 '-chiral separation method of union-2-naphthol, it is characterized in that in step 3); Said to 1; 1 '-the union-2-naphthol crude product carries out recrystallization, be with ether to 1,1 '-the union-2-naphthol crude product carries out recrystallization at least 1 time.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104164740A CN102516034A (en) | 2011-12-12 | 2011-12-12 | Chiral resolution method of racemic 1,1'-bi-2-naphthol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104164740A CN102516034A (en) | 2011-12-12 | 2011-12-12 | Chiral resolution method of racemic 1,1'-bi-2-naphthol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102516034A true CN102516034A (en) | 2012-06-27 |
Family
ID=46287175
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011104164740A Pending CN102516034A (en) | 2011-12-12 | 2011-12-12 | Chiral resolution method of racemic 1,1'-bi-2-naphthol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102516034A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102731388A (en) * | 2012-07-05 | 2012-10-17 | 广州大学 | Method for preparing (R)/(S)-6,6-dihydroxy-5,5-biquinoline |
| CN102731389A (en) * | 2012-07-05 | 2012-10-17 | 广州大学 | Synthesis method of (R)/(S)-6,6'-benzyloxyl-5,5'-biquinoline |
| CN112961037A (en) * | 2021-02-08 | 2021-06-15 | 浙江工业大学 | Method for resolving racemic chiral compound by molecular distillation method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11147862A (en) * | 1997-11-17 | 1999-06-02 | Daicel Chem Ind Ltd | New amino acid derivative and its production, and separation of optical isomer of binaphthol |
-
2011
- 2011-12-12 CN CN2011104164740A patent/CN102516034A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11147862A (en) * | 1997-11-17 | 1999-06-02 | Daicel Chem Ind Ltd | New amino acid derivative and its production, and separation of optical isomer of binaphthol |
Non-Patent Citations (2)
| Title |
|---|
| 《Chemical Communications》 19971231 Fumio Toda et al. New chiral ammonium salt hosts derived from amino acids: very efficient optical resolution of 2,2'-dihydroxy-1,1'-binaphthyl by complexation with these host compounds 1087-1088 1-9 , * |
| FUMIO TODA ET AL.: "New chiral ammonium salt hosts derived from amino acids: very efficient optical resolution of 2,2’-dihydroxy-1,1’-binaphthyl by complexation with these host compounds", 《CHEMICAL COMMUNICATIONS》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102731388A (en) * | 2012-07-05 | 2012-10-17 | 广州大学 | Method for preparing (R)/(S)-6,6-dihydroxy-5,5-biquinoline |
| CN102731389A (en) * | 2012-07-05 | 2012-10-17 | 广州大学 | Synthesis method of (R)/(S)-6,6'-benzyloxyl-5,5'-biquinoline |
| CN102731389B (en) * | 2012-07-05 | 2013-10-16 | 广州大学 | Synthesis method of (R)/(S)-6,6'-benzyloxyl-5,5'-biquinoline |
| CN102731388B (en) * | 2012-07-05 | 2013-11-27 | 广州大学 | Method for preparing (R)/(S)-6,6'-dihydroxy-5,5'-biquinoline |
| 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 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tang et al. | Equilibrium studies on enantioselective extraction of oxybutynin enantiomers by hydrophilic β‐cyclodextrin derivatives | |
| CN102516034A (en) | Chiral resolution method of racemic 1,1'-bi-2-naphthol | |
| JP6108559B2 (en) | Method for producing lignin from biomass using lignin-soluble ionic liquid, and method for producing lignin, hemicellulose, and cellulose | |
| JP2016011264A (en) | Method for manufacturing 2,5-furandicarboxylic acid | |
| RU2008137508A (en) | HUMIC DERIVATIVES, METHODS FOR PRODUCING AND USING THEM | |
| CN104289210A (en) | Preparation method of novel phenylalanine chiral chromatographic column stationary phase | |
| CN113354570A (en) | Method for efficiently extracting and separating carbazole in anthracene oil by using eutectic solvent | |
| CN101580472B (en) | Resolving agent for 1, 1'-bi-2-naphthol and resolving method thereof | |
| CN102584906A (en) | Extracting method of fulvic acid | |
| US20190316225A1 (en) | Extraction of rare earth elements and carbon rich solids from coal feedstock using ionic liquids | |
| CN100351007C (en) | Method for preparing molecular engram CS/TEOS hybridized film by separation of phenylalanine isomer | |
| Tang et al. | Experimental and model study on the multiple chemical equilibrium for reactive extraction of ibuprofen enantiomers with HP-β-CD as hydrophilic selector | |
| CN107715909A (en) | A kind of Proline-Catalyzed agent of pentaerythrite support and preparation method and application | |
| CN107721899B (en) | Eutectic solvent and preparation method thereof | |
| CN102432870A (en) | Synthesis method of dendritic complex main antioxidant | |
| CN102643236A (en) | Method for preparing chiral amide imidazolium bromide ionic liquid from natural amino acid | |
| KR100775786B1 (en) | Cardanol derivative and the method for manufacturing the same | |
| CN102675053B (en) | Method for preparing enantiopure (S)-1,1'-co-2-naphthol and enantiopure (R)-1,1'-co-2-naphthol conveniently and simply | |
| CN112058103B (en) | Cellulose grafted carboxymethyl imidazole chloride salt gas separation membrane and preparation method thereof | |
| CN117925269A (en) | Method for efficiently separating phenolic substances in oil products by adopting eutectic solvent | |
| CN112574774A (en) | Eutectic solvent, preparation method thereof and application thereof in separation of aromatic hydrocarbon | |
| Carpenter et al. | Some studies involving the use of chiral amine oxides for the enantioselective preparation of (propargyl alcohol) Co2 (CO) 5 (PR3) complexes | |
| JP2018168424A (en) | High precision mutual separation method of rare earth ions | |
| Lanitou et al. | Studies on the catalytic activity of novel hybridized chiral organo-inorganic catalysts for epoxidation and alkylation reactions | |
| CN107474001B (en) | synthetic method of α -diacetoxymethyl substituted nitrogen heterocyclic compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120627 |