【作者】 易健民；

【导师】 黄可龙；

【作者基本信息】 中南大学 ， 应用化学， 2010， 博士

【摘要】 单一光学异构体手性农药以其高效、高选择性和高安全性成为近年来研究开发的重要发展方向。拟除虫菊酯是一种重要的手性农药,合成该农药的关键问题是要从外消旋菊酸获得单一光学异构体菊酸。本文用酒石酸酯对2,2-二甲基-3-(2-甲基丙稀基)环丙烷羧酸(反式第一菊酸)、2,2-二氯-3-(2-甲基丙稀基)环丙烷羧酸(顺式、反式二氯菊酸)、2,2-二甲基-3-(2-氯—3,3,3-三氟-1-丙烯基)环丙烷羧酸(三氟氯菊酸)、3-甲基-2-(4-氯苯基)丁酸(氰戊菊酸)对映体成功地进行了手性识别萃取拆分。进而创造性地提出了双相(O／W)识别手性萃取对菊酸对映体进行手性拆分,显著地提高了分离能力。为采用手性萃取分离制备单一光学异构体菊酸提供了新的理论依据和技术基础。选用新的手性柱奎宁生物碱CHIRALPAK QN-AX (150x4.6mmID),建立了一种反相流动相HPLC法分析五种菊酸对映体的分析方法,实现了对五种对映体的基线分离,分离度大,稳定性好,适用范围广,为菊酸对映体的手性分析提供了新的方法。合成了一系列手性分离萃取剂酒石酸酯,考察了醇酸摩尔比、带水剂用量、催化剂种类和用量对合成收率的影响,得到了最佳的实验条件。以合成L-酒石酸异丁酯为例,其最佳实验条件：醇酸摩尔比为3：1,在投料15 gL-酒石酸与22.24g异丁醇的情况下,催化剂为1.0g对甲苯磺酸、带水剂为60mL甲苯,酯化反应收率可达99.5%。研究了酒石酸酯类化合物作为手性萃取剂对五种菊酸对映体的萃取分配行为,考察了影响因素,确定了最佳萃取条件,获得了萃取规律。①D型和L型酒石酸酯都能成功地将上述五种菊酸对映体进行手性萃取分离,分离因子可达1.25到1.50之间。②酒石酸酯烷基长度越大,分离因子α值越大；烷基空间位阻变大(有支链或有环状结构),分离因子α值也较大。③提高萃取剂浓度,分配系数k值相应提高,但分离因子α值先提高,达到一定峰值后又呈下降趋势。较为适宜的萃取剂浓度在0.20-0.30 mol·L-1之间。④提高水相pH值,分配系数k值呈下降趋势,分离因子α值也呈下降趋势,水相pH值以2.50-5.50为宜。⑤适宜溶剂为1,2-二氯乙烷和氯仿。在水相和有机相中分别加入疏水性酒石酸酯和水溶性环糊精衍生物构成双相(O／W)识别手性萃取体系,首次将它们用于菊酸对映体的手性分离,该方面研究未见他人文献报道。L-酒石酸异丁酯对反式第一菊酸S对映体和氰戊菊酸S对映体的识别能力大于对它们的R对映体的识别能力,而D-酒石酸异丁酯则刚好相反。羟丙基β-环糊精HP-β-CD对这两种菊酸对映体的手性识别作用与L-酒石酸异丁酯对它们的手性识别作用是一致的,是互相叠加的。因而采用合适的双相手性萃取剂极大地提高了分离能力。加入HP-β-CD后,分离因子α值可由单相萃取时的1.30、1.20提高到双相萃取时的1.70、1.80。随着L-酒石酸异丁酯浓度的增大,k值和α值均有增大；随着HP-β-CD的浓度的增大,k值和α值先增大后减少；随着pH值增大,k值和α值都降低；L-酒石酸酯烷基长度和位阻大小对k值和α值有较大影响。最佳双相体系和萃取条件以分离氰戊菊酸为例：0.30 mol·L-1L-酒石酸异丁酯,用1,2-二氯乙烷作溶剂,4.0mmol·L-1 HP-β-CD,20%的甲醇水溶液,pH为4.0左右,分离因子可达到1.80。酒石酸酯分子存在两个手性碳原子,有特殊的立体结构,有多个作用点,这些作用点与拆分对象菊酸对映体之间将会产生不同的分子间作用力,因而具有手性识别功能。β-环糊精(β-CD)的“外亲水,内疏水”的特殊环形立体结构,能与菊酸对映体分子形成包合物,且两对映体包合物稳定性存在差异从而具有手性识别功能。更多还原

【Abstract】 Single optical isomers of chiral pesticides have become an important field of research and development because of its high efficiency, high selectivity and high security. Pyrethroid is an important chiral pesticide, and the key to synthesize these pyrethroids is to obtain single optical isomers chrysanthemic acid from the itermediates of pyrethroid. A series of tartrates have been synthesized in this dissertation, and used as chiral extractants for separation of five racemic chrysanthemic acid enantiomers. Based on these, a new method, biphasic recognition chiral extraction, has been presented to separate two kinds of chrysanthemic acid enantiomers and the separation ability was improved significantly. The dissertation has provided new theory and technical basis for preparation of high-efficient but low toxicity pesticides.By using CHIRALPAK QN-AX, HPLC was established to analyze trans-chrysanthemic acid, cis-and trans-permethrinic acid, lambda-cyhalothric acid and fenvaleric acid, and the baseline separations of five enantiomers were achieved.A series of tartrates have been synthesized in this dissertation, and the factors affecting the yield of synthesis has been investigated. The best experimental conditions have been gained. Taking the synthesis of L-tartaric acid iso-butyl as an example, the best experimental conditions are that the molar rate of alcohol (22.24 g) and L-tartaric acid (15 g) is 3:1, with catalyst tosylate of 1.0 g and toluene of 60 ml.The dissertation has studied the distribution behavior of five chrysanthemic acid enantiomers with tartrate esters as chiral extractants and investigated the factors affecting the extraction performance.1) Both D-and L-tartaric acid ester can be used as chiral extractants to separate the five kinds of chrysanthemum acid enantiomers, and the seperation factor can reach at 1.25-1.5.2) Tartaric acid ester alkyl length and its steric have a certain impact on the separation factors. The larger alkyl length and alkyl steric (with branched-chain or ring structure) are, the larger separation factors are; 3) Extractant concentrations also has a greater impact on extraction performance. With the increase of extracant concentrations, the partition coefficients increase, but the separation factors first increase then decrease after up to the peak. The appropriate extractant concentrations are between 0.20-0.30 mol·L-1; 4) The partition coefficientsand the separation factors decrease with the increase of pH value. The best value of pH is between 2.50-5.50; 5) 1, 2-dichloroethane solution and chloroform will be the proper solvents.Biphasic recognition chiral extraction system has been constructed, in which two kinds of extractant with opposite recognition direction (hydrophobic D-/L-tartaric acid esters and water-soluble cyclodextrin derivatives) are added in the organic phase and water phase, respectively. This system is used to separate of two kinds of chrysanthemic acid enantiomers.β-CD derivatives have stronger recognition abilities for S-chrysanthemic acid than those for R-chrysanthemic acid, while L-tartrate derivatives have reversed recognition abilities. Thus the use of appropriate two-phase chiral extractant greatly enhances separation ability. Adding HP-β-CD, the separation factor value can be enhanced from 1.30 and 1.20 for the single-phase to 1.70 of 1.80 for two-phase extraction. Extraction conditions also have an impact on k and a. Take the separation of cyanide-chrysanthemic-acid as an example, the best separation factor is 1.80 under conditions that the concentrations of L-iso-butyl tartrate and HP-β-CD are 0.30 mol·L-1 and 4.0 mmol·L-1, respectively, with 1,2-dichloroethane as solvent containing 20% methanol solution at pH 4.0.Tartaric acid ester molecule has two chiral carbon atoms, special three-dimensional structure and multiple action spots which have different intermolecular forces with chrysanthemum acid enantiomers, thus it has the function of chiral recognition. The special three-dimensional ring structure-"hydrophilic outside, hydrophobic inside" ofβ-cyclodextrin (β-CD) can form inclusion complex with chrysanthemic acid, and the inclusion complex stability of the two enantiomers is different and thus it has the ability of chiral recognition.更多还原