The Synthesis Of Several Room Temperature Ionic Liquids And Application In Chromatographic Analysis

The room temperature ionic liquids (ILs or IL) refer to a group of organic salts that are liquids at room temperature. In recent years, studies focusing on ILs have sprung up.With their attracting property increasing universally realized, great progress are being made in the the synthetic approach of ILs and much more new ion have been exploited. As one new material, ILs has been successfully used in electrochemistry, asymmetric synthesis, isolation and extraction, catalysis.In this paper, the synthesis route of ILs was studied and optimized. Then, the application of the chiral ILs was extended to chromatographic analysis field:enantioseparatfon of rabeprazole and omeprazole was achieved in nonaqueous capillary electrophoresis (NACE). The influences of separation conditions including the composition of organic solvent, the concentration of chiral ILs, pH were evaluated. The mechanism of enantioseparation was discussed; the binary system consists of chiral ILs and cyclodextrin (CD) was evaluated and the effect of chiral ILs on the binary system was studied; A high performance liquid chromatographic(HPLC)method for separation of five drugs was established. The five drugs:metoprolol, bisoprolol, propranolol, omeprazole, ketoprofen were successful separated. The separation mechanism of ephedrine-based ILs was discussed; A TLC method was established for the separation of candidate medicine I and analog substances. The main contents were as follows:1.The synthesis study of ILsThe 1-butyl-3methyl-imidzole tetrafluoroborate ILs was synthesized by microwavation and metathetical reaction method and the aforementioned two methods were compared; the ephedrine-based ILs [DMP][Tf2N] was synthesized by metathetical reaction and the synthetic approach was optimized. The 1-butyl-3-methyl-imidazole phenylalanine ILs [Bmim][Phe], 1-butyl-3-methyl-imidazole raline [Bmim][Pro] and glycine-hexafluorophosphoric ILs [Gly][PF6] were synthesized by acid-base reaction. For all the synthesizd ILs, study was carried out to confirm their structure and physical and chemical properties such as solubility, the maximum absorption wavelength of ILs was investigated.2. Chiral ionic liquids [DMP][Tf2N] for enantioseparation by nonaqueous capillary electrophoresisIn this paper, we first developed a method utilizing [DMP][Tf2N] as both chiral selector in NACE. Enantioseparation of rabeprazole and omeprazole was achieved in acetonitrile-methanol (60:40 v/v) containing 60 mM [DMP][Tf2N] as chiral selector. The influences of separation conditions including the composition of organic solvent, the concentration of IL, pH were evaluated. Both ion-pairs interaction and the hydrogen bonding interaction were responsible for main interaction mechanism.3. The influence of [Bmim][Phe] on CD-based enantioseparation systemIn this study, we developed binary system consisting of the chiral ILs and HP-β-CD. Enantioseparations of amlodipine and homatropine methylbromide were achieved in the BGE containing sodium dihydrogen phosphate 75 mmol·L-1 pH=2.50, HP-β-CD 20 mmol·L-1 and sodium dihydrogen phosphate 75 mmol·L-1 pH=2.50, HP-β-CD 10 mmol·L-1, respectively. On the basis of this, [Bmim][Phe] was introduced in the CD-based enantioseparation system. The binary system was evaluated by parameters such as resolution (R) and number of theoretical plates (n). The results showed that [Bmim][Phe] had great effect on electroosmotic flow which was benefit for enantioseparation indirectly. However, the synergistic effect between [Bmim][Phe] and CD was not obvious.4. [DMP][Tf2N] for separation of five drugs in HPLC and its chromatographic effect study The application of [DMP][Tf2N] as additive in HPLC has not been reported until now. A C18 column was used with the mixture of methanol-water 6:4 (v/v, pH=4.0,5 mmol·L-1[DMP][Tf2N] as mobile phase. The five drugs:metoprolol,bisoprolol propranolol, omeprazole, ketoprofen were successful separated. The effect of concentration of [DMP][Tf2N],pH, and the variety of anion on separation was discussed. The results showed that the adoptd ILs shorten the retention time of acidic analytes, while extended the retention time for base analytes. Both the cation and anion have a significant influence on chromatographic behavior of the analytes.5. Separation of candidate medicine I and analog substances using [Bmim][BF4]by TLC[Bmim][BF4] was used to separate candidate medicine I and analog substances by TLC.The factors such as the selection of development system, the type and concentration of the ILs, the type and concentration of the acid and base of the development system were studied. The four drugs can be separated completely in the optimized condition. The proposed method was established to be simple, rapid and reproducible. The main separation mechanism of [Bmim][BF4]in TLC was related to shield the silanol groups.