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利用热力学方法研究甘氨酸和氯化镁-乙醇加合物结晶动力学
ZIAUL HAQUE ANSARI
Thesis Advisor李志宝
2018-07
Degree Grantor中国科学院研究生院
Degree Name博士
Degree Discipline化学工程
Keyword模拟,甘氨酸,多形性,氯化镁-乙醇加合物,结晶动力学
Abstract

甘氨酸是一个重要的有机组分,广泛用于食品、制药、化学和农业工业中。 生物化工中的分离方法包括分步沉淀、结晶和离子交换等,分离成本占总制备成本的50%以上。为了开发更高效的分离方法,在不同介质、温度和浓度中, 进行热力学性质研究是非常有必要的。晶体产品的晶型控制在制药方面也十分关键,因为错误晶型的采用将会导致危险。因此, 我们对甘氨酸成核、生长以及不同溶剂介质中的晶型转变可能为其多晶型的筛选提供基础。本论文的研究成果对理解其他氨基酸的多晶型也有重要的意义。以MgCl2为载体的多相Ziegler?Natta催化剂是用于聚丙烯的聚合反应的。MgCl2首先利用醇类处理(多用乙醇),然后注入TiCl4。前驱体中MgCl2/EtOH的比例的决定了得到的聚合体的活度和等规度。MgCl2?nEtOH的结晶动力学有助于更深入理解从而控制结晶加合物的结构。首先, 我们采用动态法测定了甘氨酸(a晶型)在不同溶液中的溶解度。在电解质溶液中,测定了甘氨酸在温度为283.15?333.15 K, MgCl2浓度为0.5到3.5 mol?kg?1时在MgCl2?H2O溶液中的溶解度,以及MgCl2浓度为0.5、1.0和 1.5 mol?kg?1时在NaCl?MgCl2?H2O溶液中的溶解度。在酸溶液中,测定了温度为283.15-343.15 K, HCl浓度在 4.0 mol?kg?1以下时,甘氨酸在盐酸溶液中的溶解度,以及MgCl2浓度为0.25、0.5和0.75 mol?kg?1时在HCl?MgCl2混合溶液中的溶解度。在醇溶液中,测定了甘氨酸在温度为283.15?333.15 K时在乙醇/正丙醇- H2O溶液中,以及NaCl 浓度为0.5、 1.0和2.0 mol?kg?1时在乙醇?NaCl?H2O溶液,和NaCl 浓度为0.5 mol?kg?1时在正丙醇?NaCl?H2O溶液中的溶解度。研究发现随着温度的升高和溶液浓度的增大,甘氨酸的溶解度在MgCl2 和HCl溶液中有大幅度提高,在MgCl2?NaCl 和HCl?MgCl2溶液中提高幅度中等,而在醇溶液(乙醇/正丙醇)则有所降低。此外,还测定了MgCl2.6H2O在甘氨酸-水中的溶解度以及NaCl在醇(乙醇/正丙醇)?甘氨酸?H2O中的溶解度测定的所有实验数据都采用OLI软件进行了热力学模拟。首先利用OLI软件中的Stream Analyzer对所有的三组体系的溶解度进行了预测,发现有很大的偏差。采用Bromley?Zemaitis (B?Z)和Mixed Solvent Electrolytes (MSE)两组模型利用环境模拟程序对溶解度数据进行了回归。B?Z模型用于混合电解质体系(甘氨酸?MgCl2?NaCl?H2O),MSE模型用于混合溶剂体系(甘氨酸?HCl?MgCl2?H2O)和(甘氨酸?醇 (乙醇/正丙醇)?NaCl?H2O)。利用新获得的参数能够成功计算不同体系的溶解度数据,绝对误差值很小。通过从甘氨酸?HCl?MgCl2?H2O体系得到的新参数计算得到了甘氨酸在不同介质(H2O, MgCl2?H2O, HCl?H2O, HCl?MgCl2?H2O)和不同浓度范围的过饱和度。同时也得到了不同温度下MgCl2?6C2H5OH在MgCl2?6C2H5OH溶液的过饱和度。这些结果是通过OLI Stream Analyzer元件进行计算得到的。通过实验研究了a-甘氨酸在不同溶液中的晶型转化情况,包括在水溶液中、在MgCl2 (1.5 mol?kg?1)?H2O、HCl (1.0 mol?kg?1)?H2O、NaOH (1.0 mol?kg?1)?H2O、glycine–HCl (1.0 mol?kg?1)–MgCl2 (0.75 mol?kg?1)–H2O、和glycine–HCl (2.0 mol?kg?1)–MgCl2 (1.5 mol?kg?1)–H2O体系中。每种溶液加热到70 °C然后冷却,保持一定的过饱和度直至晶体析出。采用这种方式考察了介质、温度、过饱和度和时间对甘氨酸结晶的影响。只有在HCl溶液中在整个实验温度和时间范围内能够得到纯的g-甘氨酸。除了在HCl溶液中,其他体系都会生成a-甘氨酸或者a-甘氨酸和g-甘氨酸混合物,具体产物会与条件相关。在晶体形貌的考察中发现a-甘氨酸在纯水中呈现棱柱状,g-甘氨酸在MgCl2溶液中是柱状,g-甘氨酸在HCl溶液中呈现双锥体和柱状结构,g-甘氨酸在NaOH溶液中呈现NaOH双锥体,在HCl–MgCl2混合溶液中呈现双锥体和柱状结构的混合物。实验研究了MgCl2?乙醇加合物的结晶介稳区(MZW)和诱导期。两者都采用多温的方法进行测定, 并采用Nyvlt和Sangwal方法计算了结晶动力学。考察了温度和过饱和度对结晶诱导期的影响。发现诱导期随着温度和过饱和度的增大而减小。均相成核和非均相成和依赖于诱导期随温度和过饱和度的变化。通过诱导期数据计算了界面张力和其它各种成核参数。;Glycine is an important organic compound used in food, pharmaceutical, chemical, and agricultural industries. The separation process used in biochemical industries such as, fractional precipitation, crystallization, and ion exchange are conventional, and the cost associated in these processes is almost 50 % higher than the total cost of manufacturing. To develop efficient separation techniques, a thorough knowledge of thermodynamic properties in different medium, and at different temperatures and concentrations are essential. Polymorph control of the crystalline products is important especially in pharmaceutical industries where a wrong polymorph of a drug can pose a danger. Study for nucleation and growth/polymorphic transformation of glycine in different media will provide insight into the riddle of glycine polymorphism. The study will be useful in understanding polymorphism for other amino acids. MgCl2 supported heterogeneous Ziegler?Natta catalyst is used in the polymerization reaction in the polyolefin industries. MgCl2 is first treated with alcohol (mostly ethanol) and then TiCl4 is impregnated on it. The MgCl2/EtOH ratios in the precursor determine, among other features, the activity and the isotacticity degree of the resulting polymer. The crystallization kinetics of MgCl2?nEtOH will contribute to a deeper understanding, and thereby to a greater control, of the structure of crystalline adduct. The solubility determination by dynamic method was carried out of glycine (a-form) in different solutions. In electrolyte solutions, the solubility of glycine in MgCl2?H2O solutions from molality 0.5 to 3.5 and in mixed NaCl?MgCl2 solutions at MgCl2 (0.5, 1.0, and 1.5 mol?kg?1) from 283.15 to 333.15 K were carried out. In acid solutions, the solubility of glycine in HCl?H2O upto molality 4.0 and in mixed HCl?MgCl2 solutions at MgCl2 (0.25, 0.5, and 0.75 mol?kg?1) from 283.15 to 343.15 K were carried out. In alcohol solutions, the solubility of glycine in alcohol (ethanol/1-propanol)?H2O, in ethanol?NaCl?H2O solutions at NaCl (0.5, 1.0, and 2.0 mol?kg?1) and 1-propanol?NaCl?H2O solutions at NaCl (0.5 mol?kg?1) from 283.15 to 333.15 K were carried out. The solubilities of glycine in MgCl2 and HCl solutions show large increment, in mixed systems MgCl2?NaCl and HCl?MgCl2 solutions show moderate increase and in alcohol (ethanol/1-propanol) solutions show decrease in solubility with increasing temperature and concentration. Also, solubilities study for bischofite (MgCl2?6H2O) in glycine?H2O, and NaCl in alcohol (ethanol/1-propanol)?glycine?H2O were measured. The OLI System Software was used to thermodynamically model all the systems that were measured in the laboratory. Initial predictions by Stream Analyzer for all the three systems showed large deviations from the experimental data. Environmental Simulation Program was used to regress the solubility data by two different models, Bromley?Zemaitis (B?Z), and Mixed solvent electrolytes (MSE) model. B?Z model was used in mixed electrolyte (glycine?MgCl2?NaCl?H2O), and MSE model was used in mixed solvent (glycine?HCl?MgCl2?H2O) and glycine?alcohol (ethanol/1-propanol)?NaCl?H2O systems. Newly obtained model parameters were successful in representing the respective systems with low average absolute deviations. Supersaturations for glycine in different media (H2O, MgCl2?H2O, HCl?H2O, HCl?MgCl2?H2O) at different concentrations level were obtained with the aid of newly obtained model parameters from glycine?HCl?MgCl2?H2O systems. Supersaturation for MgCl2?6C2H5OH in MgCl2?6C2H5OH solutions were also obtained at different temperatures. These calculations were obtained with the aid of OLI Stream Analyzer.Polymorphic transformation of a-glycine was experimentally studied in different solutions, such as H2O, MgCl2 (1.5 mol?kg?1)?H2O, HCl (1.0 mol?kg?1)?H2O, NaOH (1.0 mol?kg?1)?H2O, glycine–HCl (1.0 mol?kg?1)–MgCl2 (0.75 mol?kg?1)–H2O, and glycine–HCl (2.0 mol?kg?1)–MgCl2 (1.5 mol?kg?1)–H2O systems. The respective solutions were heated to 70°C and then cooled and hold at different supersaturation level until the crystallization. In this way, the effects of medium, temperature, supersaturation, and time on the crystallization of glycine were investigated. Single g-glycine phase was achieved only in the HCl solution under all the investigated temperature and holding time. In the NaOH solution, g-glycine phase was observed at certain conditions. In other systems, such as H2O, MgCl2 (1.5 mol?kg?1)?H2O, and HCl?MgCl2 (1.5 mol?kg?1, 2.0 mol?kg?1)?H2O, a-glycine or its mixture with g-glycine or C4H18N2O4·HCl was produced depending on the conditions. Morphological investigation showed a-glycine with prismatic shape in pure water, g-glycine with polar morphology in MgCl2 solution, g-glycine with bipyramid and polar structure in HCl solution, g-glycine with bipyramid shape in NaOH solution, and combination of bipyramid and polar shapes crystals formed in HCl?MgCl2 mixed system. An experimental study was carried out to determine the metastable zone width (MSZW) and induction time for the crystallization of MgCl2?ethanol adduct. The metastable zone (MSZW) width and induction period were measured by polythermal method at various temperatures. The crystallization kinetics was calculated by Nyvlt and Sangwal approach. The effect of temperature, and supersaturation were studied by the induction time measurement. It was observed that induction period decreases as either temperature or supersaturation increases. The homogeneous and heterogeneous mechanisms were identified by the dependence of the induction period on temperature and supersaturation. From the induction period data, the interfacial energy and other various nucleation parameters were calculated. 

Language中文
Document Type学位论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/26895
Collection中国科学院过程工程研究所
研究所(批量导入)
Recommended Citation
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ZIAUL HAQUE ANSARI. 利用热力学方法研究甘氨酸和氯化镁-乙醇加合物结晶动力学[D]. 中国科学院研究生院,2018.
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