CN103664998B - The resolution reagent of separation of ofloxacin racemic mixture and method - Google Patents
The resolution reagent of separation of ofloxacin racemic mixture and method Download PDFInfo
- Publication number
- CN103664998B CN103664998B CN201310646799.7A CN201310646799A CN103664998B CN 103664998 B CN103664998 B CN 103664998B CN 201310646799 A CN201310646799 A CN 201310646799A CN 103664998 B CN103664998 B CN 103664998B
- Authority
- CN
- China
- Prior art keywords
- separation
- ofloxacine usp
- tartaric acid
- concentration
- ofloxacin
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
Abstract
The invention discloses a kind of resolution reagent and method of separation of ofloxacin racemic mixture.Separation of ofloxacin racemic mixture and alkyl imidazole L-TARTARIC ACID ionic liquid are dissolved in deionized water and form aqueous phase, D-dibenzoyl tartaric acid is dissolved in nonylcarbinol simultaneously and forms organic phase, organic phase and aqueous phase are mixed and puts into vibrator, concussion, leave standstill, water intaking phase clear liquid detects the concentration of Levofloxacin and D-Ofloxacine USP 23, in organic phase, the concentration of Levofloxacin and D-Ofloxacine USP 23 obtains each via mass conservation law, calculate the partition ratio of Levofloxacin and D-Ofloxacine USP 23 respectively, and then calculating separation factor, separating effect is better, split successfully.The present invention utilizes ionic liquid alkyl imidazole L-TARTARIC ACID ionic liquid and D-dibenzoyl tartaric acid jointly to split separation of ofloxacin racemic mixture, improves the efficiency split, and reduce and split required reagent, operating procedure is simple, and selectivity is high, and suitability for industrialized is produced.
Description
Technical field
The present invention relates to chiral drug chemical separation, particularly relate to a kind of resolution reagent and method of separation of ofloxacin racemic mixture.
Background technology
Separation of ofloxacin racemic mixture is a kind of fluoroquinolones of broad-spectrum antimicrobial.The oral easy absorption of separation of ofloxacin racemic mixture, its mechanism of action is the DNA gyrase of anti-bacteria, and clinical application is evident in efficacy.Levofloxacin is the one in separation of ofloxacin racemic mixture chiral isomer.Levofloxacin has more advantage than separation of ofloxacin racemic mixture, and its anti-microbial activity is 2 times of separation of ofloxacin racemic mixture, and water-soluble is 8 times of separation of ofloxacin racemic mixture, and its toxic side effect is less.
The separation factor of enantiomer investigates an important factor of chiral separation effect, it is defined as the ratio of two kinds of isomer partition ratios, in general, when separation factor is 1, illustrate that two kinds of isomer are not separated, separation factor departs from 1 larger, then illustrate that two kinds of separated degree of configuration material are larger.Tang's text (Tang's text, Zhou Chunshan, Journal of Chemical Industry and Engineering, 2003, V200,1729-1732) utilizes hydrophobicity L-TARTARIC ACID ester to be separated separation of ofloxacin racemic mixture, and the separation factor of fractionation is between 1.06-1.26.Subsequently, Tang's text (Tang's text, Chen Guobin, Yi Jianmin, Zhang Weizhen, chemical journal, 2004, V62,1621-1625) adopts again the method for chiral ligand permutoid reaction to split separation of ofloxacin racemic mixture, and the separation factor of fractionation is generally less than 1.4.Peng Xiahui etc. (Peng Xiahui, Huang Kelong, in Buddha's warrior attendant, Zhao Xuehui, Central South University's journal (natural science edition), 2006, V3,527-531) adopt emulsion liquid film chiral separation separation of ofloxacin racemic mixture, its separation factor is below 1.35.Various method for splitting used at present, its separation factor is all within 1.4, and separation of ofloxacin racemic mixture splits difficult, is unfavorable for industrial application.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, a kind of resolution reagent and method of separation of ofloxacin racemic mixture is provided.
The resolution reagent of separation of ofloxacin racemic mixture is made up of two kinds of materials, be respectively the D-dibenzoyl tartaric acid in organic phase nonylcarbinol, alkyl imidazole L-TARTARIC ACID ionic liquid in aqueous phase, the cationic molecular structural formula of described alkyl imidazole L-TARTARIC ACID ionic liquid is:
R=C
nH
2n+1
The molecular structural formula of described alkyl imidazole L-TARTARIC ACID ionic liquid anion structure is:
Described alkyl imidazole L-TARTARIC ACID ionic liquid is: 1-ethyl-3-methylimidazole L-TARTARIC ACID salt, 1-butyl-3-Methylimidazole L-TARTARIC ACID salt, 1-hexyl-3-Methylimidazole L-TARTARIC ACID salt, 1-octyl group-3-Methylimidazole L-TARTARIC ACID salt or 1-decyl-3-Methylimidazole L-TARTARIC ACID salt.
The method for splitting of separation of ofloxacin racemic mixture is, separation of ofloxacin racemic mixture and alkyl imidazole L-TARTARIC ACID ionic liquid are dissolved in deionized water formed containing alkyl imidazole L-TARTARIC ACID ionic liquid concentration be the aqueous phase of 0.05-0.5mol/L, D-dibenzoyl tartaric acid is dissolved in formation in nonylcarbinol is the organic phase of 0.2-0.5mol/L containing D-dibenzoyl tartaric acid concentration simultaneously, be that organic phase and the aqueous phase of 1:1-1:10 mixes and put into vibrator by volume ratio, concussion 2-4h, leave standstill, water intaking phase clear liquid detects the concentration of Levofloxacin and D-Ofloxacine USP 23, in organic phase, the concentration of Levofloxacin and D-Ofloxacine USP 23 obtains each via mass conservation law, calculate the partition ratio of Levofloxacin and D-Ofloxacine USP 23 respectively, and then calculating separation factor, separating effect is better, split successfully, wherein, Levofloxacin concentration in Levofloxacin concentration/aqueous phase in Levofloxacin partition ratio=organic phase, D-Ofloxacine USP 23 concentration in D-Ofloxacine USP 23 concentration/aqueous phase in D-Ofloxacine USP 23 partition ratio=organic phase, separation factor=Levofloxacin partition ratio/D-Ofloxacine USP 23 partition ratio.
The present invention utilizes chiral ionic liquid alkyl imidazole L-TARTARIC ACID ionic liquid and D-dibenzoyl tartaric acid jointly to split separation of ofloxacin racemic mixture, its separation factor can reach 3.17, improve the efficiency of chiral separation to a great extent, reduce and split required reagent, operating procedure is simple, selectivity is high, and suitability for industrialized is produced.
Embodiment
The resolution reagent of separation of ofloxacin racemic mixture is made up of two kinds of materials, be respectively the D-dibenzoyl tartaric acid in organic phase nonylcarbinol, alkyl imidazole L-TARTARIC ACID ionic liquid in aqueous phase, the cationic molecular structural formula of described alkyl imidazole L-TARTARIC ACID ionic liquid is:
R=C
nH
2n+1
The molecular structural formula of described alkyl imidazole L-TARTARIC ACID ionic liquid anion structure is:
Described alkyl imidazole L-TARTARIC ACID ionic liquid is: 1-ethyl-3-methylimidazole L-TARTARIC ACID salt, 1-butyl-3-Methylimidazole L-TARTARIC ACID salt, 1-hexyl-3-Methylimidazole L-TARTARIC ACID salt, 1-octyl group-3-Methylimidazole L-TARTARIC ACID salt or 1-decyl-3-Methylimidazole L-TARTARIC ACID salt.
The method for splitting of separation of ofloxacin racemic mixture is, separation of ofloxacin racemic mixture and alkyl imidazole L-TARTARIC ACID ionic liquid are dissolved in deionized water formed containing alkyl imidazole L-TARTARIC ACID ionic liquid concentration be the aqueous phase of 0.05-0.5mol/L, D-dibenzoyl tartaric acid is dissolved in formation in nonylcarbinol is the organic phase of 0.2-0.5mol/L containing D-dibenzoyl tartaric acid concentration simultaneously, be that organic phase and the aqueous phase of 1:1-1:10 mixes and put into vibrator by volume ratio, concussion 2-4h, leave standstill, water intaking phase clear liquid detects the concentration of Levofloxacin and D-Ofloxacine USP 23, in organic phase, the concentration of Levofloxacin and D-Ofloxacine USP 23 obtains each via mass conservation law, calculate the partition ratio of Levofloxacin and D-Ofloxacine USP 23 respectively, and then calculating separation factor, separating effect is better, split successfully.
Embodiment 1
Separation of ofloxacin racemic mixture and 1-ethyl-3-methylimidazole L-TARTARIC ACID salt are dissolved in deionized water formed containing 1-ethyl-3-methylimidazole L-TARTARIC ACID salt concn be 0.05mol/L, separation of ofloxacin racemic mixture concentration is the aqueous phase of 1000ppm, D-dibenzoyl tartaric acid is dissolved in formation in nonylcarbinol is the organic phase of 0.2mol/L containing D-dibenzoyl tartaric acid concentration simultaneously, be that organic phase and the aqueous phase of 1:1 mixes and put into vibrator by volume ratio, concussion 2h, leave standstill, water intaking phase clear liquid detects the concentration of Levofloxacin and D-Ofloxacine USP 23 respectively, separation factor reaches 3.17.
Embodiment 2
Separation of ofloxacin racemic mixture and 1-ethyl-3-methylimidazole L-TARTARIC ACID salt are dissolved in deionized water formed containing 1-ethyl-3-methylimidazole L-TARTARIC ACID salt concn be 0.5mol/L, separation of ofloxacin racemic mixture concentration is the aqueous phase of 1000ppm, D-dibenzoyl tartaric acid is dissolved in formation in nonylcarbinol is the organic phase of 0.2mol/L containing D-dibenzoyl tartaric acid concentration simultaneously, be that organic phase and the aqueous phase of 1:1 mixes and put into vibrator by volume ratio, concussion 2h, leave standstill, water intaking phase clear liquid detects the concentration of Levofloxacin and D-Ofloxacine USP 23 respectively, and separation factor reaches 1.9.
Embodiment 3
Separation of ofloxacin racemic mixture and 1-ethyl-3-methylimidazole L-TARTARIC ACID salt are dissolved in deionized water formed containing 1-ethyl-3-methylimidazole L-TARTARIC ACID salt concn be 0.05mol/L, separation of ofloxacin racemic mixture concentration is the aqueous phase of 1000ppm, D-dibenzoyl tartaric acid is dissolved in formation in nonylcarbinol is the organic phase of 0.5mol/L containing D-dibenzoyl tartaric acid concentration simultaneously, be that organic phase and the aqueous phase of 1:10 mixes and put into vibrator by volume ratio, concussion 4h, leave standstill, water intaking phase clear liquid detects the concentration of Levofloxacin and D-Ofloxacine USP 23 respectively, separation factor reaches 2.01.
Embodiment 4
Separation of ofloxacin racemic mixture and 1-ethyl-3-methylimidazole L-TARTARIC ACID salt are dissolved in deionized water formed containing 1-ethyl-3-methylimidazole L-TARTARIC ACID salt concn be 0.05mol/L, separation of ofloxacin racemic mixture concentration is the aqueous phase of 1000ppm, D-dibenzoyl tartaric acid is dissolved in formation in nonylcarbinol is the organic phase of 0.2mol/L containing D-dibenzoyl tartaric acid concentration simultaneously, be that organic phase and the aqueous phase of 1:10 mixes and put into vibrator by volume ratio, concussion 2h, leave standstill, water intaking phase clear liquid detects the concentration of Levofloxacin and D-Ofloxacine USP 23 respectively, separation factor reaches 1.79.
Claims (2)
1. the resolution reagent of a separation of ofloxacin racemic mixture, it is characterized in that it is made up of two kinds of materials, be respectively D in organic phase nonylcarbinol ?dibenzoyl tartaric acid, alkyl imidazole L in aqueous phase ?tartrate ion liquid, described alkyl imidazole L ?the molecular structural formula of tartrate ion liquid cation be:
R＝C
nH
2n+1
Described alkyl imidazole L ?tartrate ion liquid be: 1 ?Yi Ji ?3 ?Methylimidazole L ?tartrate, 1 ?Ding Ji ?3 ?Methylimidazole L ?tartrate, 1 ?Ji Ji ?3 ?Methylimidazole L ?tartrate, 1 ?Xin Ji ?3 ?Methylimidazole L ?tartrate or 1 ?Gui Ji ?3 ?Methylimidazole L ?tartrate.
2. one kind uses the method for splitting of the separation of ofloxacin racemic mixture of reagent as claimed in claim 1, it is characterized in that, by separation of ofloxacin racemic mixture and alkyl imidazole L ?tartrate ion liquid be dissolved in deionized water formed containing alkyl imidazole L ?tartrate ion strength of fluid be 0.05 ?the aqueous phase of 0.5mol/L, simultaneously by D ?dibenzoyl tartaric acid be dissolved in nonylcarbinol formed containing D ?dibenzoyl tartaric acid concentration be 0.2 ?the organic phase of 0.5mol/L, be that organic phase and the aqueous phase of 1:1-1:10 mixes and put into vibrator by volume ratio, shake 2 ?4h, leave standstill, water intaking phase clear liquid detect L ?Ofloxacine USP 23 and D ?the concentration of Ofloxacine USP 23, in organic phase L ?Ofloxacine USP 23 and D ?the concentration of Ofloxacine USP 23 obtain each via mass conservation law, calculate respectively L ?Ofloxacine USP 23 and D ?the partition ratio of Ofloxacine USP 23, and then calculating separation factor, separating effect is better, split successfully, wherein, L ?in Ofloxacine USP 23 partition ratio=organic phase L ?in Ofloxacine USP 23 concentration/aqueous phase L ?Ofloxacine USP 23 concentration, D ?in Ofloxacine USP 23 partition ratio=organic phase D ?in Ofloxacine USP 23 concentration/aqueous phase D ?Ofloxacine USP 23 concentration, separation factor=L ?Ofloxacine USP 23 partition ratio/D ?Ofloxacine USP 23 partition ratio.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310646799.7A CN103664998B (en) | 2013-10-28 | 2013-12-04 | The resolution reagent of separation of ofloxacin racemic mixture and method |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310518280.0 | 2013-10-28 | ||
| CN2013105182800 | 2013-10-28 | ||
| CN201310518280 | 2013-10-28 | ||
| CN201310646799.7A CN103664998B (en) | 2013-10-28 | 2013-12-04 | The resolution reagent of separation of ofloxacin racemic mixture and method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103664998A CN103664998A (en) | 2014-03-26 |
| CN103664998B true CN103664998B (en) | 2016-03-30 |
Family
ID=50303862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310646799.7A Active CN103664998B (en) | 2013-10-28 | 2013-12-04 | The resolution reagent of separation of ofloxacin racemic mixture and method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103664998B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105037387B (en) * | 2015-05-25 | 2017-07-04 | 北京化工大学 | A kind of method of liquid-liquid-solid Extraction resolution Ofloxacin chiral drug |
| CN106749322B (en) * | 2015-11-23 | 2020-11-27 | 中美华世通生物医药科技（武汉）有限公司 | Process for separating enantiomers of ofloxacin |
| CN105823851A (en) * | 2015-12-15 | 2016-08-03 | 浙江海洋学院 | Detection method for ofloxacin enantiomer in seawater |
| CN107216342A (en) * | 2017-06-08 | 2017-09-29 | 武汉励合生物医药科技有限公司 | A kind of synthesis technique of Ofloxacin |
| CN107353252A (en) * | 2017-08-03 | 2017-11-17 | 辽宁大学 | A kind of ionic liquid with carboxylic acid and its preparation method and application |
| CN111925380A (en) * | 2019-05-13 | 2020-11-13 | 北京化工大学 | Combined eutectic guest resolving agent causing chiral selective transformation and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687979A (en) * | 2007-07-26 | 2010-03-31 | 味之素株式会社 | Resin composition |
| CN102351810A (en) * | 2011-08-17 | 2012-02-15 | 浙江永合化工有限公司 | Resolution method of levocetirizine chiral intermediates |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011076935A (en) * | 2009-09-30 | 2011-04-14 | Dainippon Printing Co Ltd | Dye-sensitized solar cell, liquid for electrolyte layer formation, and solar cell module |
-
2013
- 2013-12-04 CN CN201310646799.7A patent/CN103664998B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687979A (en) * | 2007-07-26 | 2010-03-31 | 味之素株式会社 | Resin composition |
| CN102351810A (en) * | 2011-08-17 | 2012-02-15 | 浙江永合化工有限公司 | Resolution method of levocetirizine chiral intermediates |
Non-Patent Citations (8)
| Title |
|---|
| A greener, halide-free approach to ionic liquid synthesis;Jamie L. Ferguson,等;《Pure and Applied Chemistry》;20111208;第84卷(第3期);723-744 * |
| Guang-nan Ou,等.Ionic liquid buffers:a new class of chemicals with potential for controlling pH in non-aqueous media.《Chemical Communications》.2006,(第44期),4626-4628. * |
| Synthesis of chiral ionic liquids by ion cross-metathesis: en route to enantioselective water-ionic liquid extraction (EWILE), an eco-friendly variant of the ELLE process;Viacheslav Zgonnik,等;《Chemical Communications》;20120202;第48卷(第26期);3185–3187 * |
| Tartrate-based ionic liquids: unified synthesis and characterisation;Anne Rouch,等;《RSC Advances》;20121002;第3卷(第2期);413-426 * |
| The effect of chiral solvent and various kinds of chiral organic salts on the asymmetric hydrogenation of methyl acetoacetate over an improved tartaric acid modified Raney nickel catalyst;Chaofeng Wang,等;《Reaction Kinetics and Catalysis Letters》;20081231;第95卷(第1期);129-134 * |
| 唐课文，等.疏水性L_酒石酸酯萃取分离氧氟沙星对映体.《化工学报》.2003,第54卷(第12期),1729-1732. * |
| 手性溶液萃取分离氧氟沙星对映体;唐课文，等;《药学学报》;20021231;第37卷(第12期);967-970 * |
| 混合萃取剂拆分氧氟沙星外消旋体;王林生，等;《分析科学学报》;20100831;第26卷(第4期);445-447 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103664998A (en) | 2014-03-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103664998B (en) | The resolution reagent of separation of ofloxacin racemic mixture and method | |
| CN103709176B (en) | Ionic liquid and L-dibenzoyl tartaric acid is utilized jointly to split reagent and the method for separation of ofloxacin racemic mixture | |
| MX2011007862A (en) | Amino-heterocyclic compounds used as pde9 inhibitors. | |
| HRP20200666T1 (en) | Pyridin-2(1h)-one quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors | |
| CN102775476A (en) | Preparation method of micafungin sodium | |
| GB2505859A8 (en) | Aripiprazole type I microcrystal, aripiprazole solid preparation, and preparation method | |
| MX360032B (en) | Granular functionalized silica, process for preparation thereof and use thereof. | |
| WO2015082422A3 (en) | Process for reacting chemical compounds | |
| Wan et al. | A 3D porous luminescent terbium metal-organic framework for selective sensing of F− in aqueous solution | |
| CN106018634A (en) | Method for adsorbing and desorbing six phenoxy carboxylic acid herbicides in water with nitrate-type layered double hydroxides (LDHS) adsorbent | |
| CN103611466B (en) | A kind of preparation method of no-salt surfactant viscoelastic solution | |
| WO2014060640A8 (en) | A process for the preparation of ospemifene | |
| WO2014024149A3 (en) | Process for the colloidal synthesis of lithium iron phosphate | |
| WO2010000357A3 (en) | Use of ionic liquids containing tricyanomethide anions as solvent for extracting alcohols from aqueous solutions | |
| Ghosh et al. | Adsorption of Fluoroquinolone Antibiotics at the Gas–Liquid Interface Using Ionic Surfactants | |
| CN103333049A (en) | Catalysis of styrene oxide alcoholysis ring-opening reaction by phosphotungstic acid ionic liquid | |
| CN102728402A (en) | Synthetic propylene carbonate catalyst, preparation method and application thereof | |
| GB201011715D0 (en) | Process for removal of fluoroorganic anions from aqueous solutions | |
| MX363186B (en) | Branched aliphatic acid as liquid cation exchangers. | |
| CN105510511B (en) | HPLC (High Performance Liquid Chromatography) separation and detection method of 2-aminobutanol enantiomer | |
| CN102928452B (en) | A kind of assay method of imidazole type ion liquid negative ion hydrogen bond Forming ability | |
| CN104897785A (en) | Method for detection of flumequine chiral enantiomers in aquatic products | |
| PL402385A1 (en) | New monofunctional poly(diallyldimethylammonium herbicidal ionic liquids), process for their preparation and use as herbicides | |
| FR3018999B1 (en) | HERBICIDE COMPOSITION, PREPARATION METHOD AND USE THEREOF | |
| CN104324684A (en) | Preparation method of mesoporous flower-cluster-shaped [gamma]-TiP and fluorine-removing application method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 210000 New Village of Yaohua Menyao'an, Qixia District, Nanjing City, Jiangsu Province Co-patentee after: Zhejiang University Patentee after: China Construction Installation Group Co., Ltd. Address before: 210000 New Village of Yaohua Menyao'an, Qixia District, Nanjing City, Jiangsu Province Co-patentee before: Zhejiang University Patentee before: China Construction Industrial Equipment Installation Co., Ltd. |