Efficient separation of enantiomers by preferential crystallization in two coupled vessels

The focus of this work is to study the enantioseparation of conglomerate forming systems using an innovative configuration for preferential crystallization. Two batch crystallizers are coupled by an exchange of their liquid phases. In each vessel one of the two enantiomers is seeded initially and crystallizes subsequently. Compared with conventional single batch crystallization the exchange of the crystal free liquid phases between two crystallizers leads to an increase of the concentrations of the preferred enantiomers and therefore to an increase of the driving forces for the crystallization. This enhances the productivity of the process compared with the conventional operation. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

优先结晶法纯化曲克芦丁

以含量81%的曲克芦丁为原料,采用优先结晶法纯化曲克芦丁。利用正交实验研究了溶剂种类,静置时间和析晶温度对纯化结果的影响。实验说明,150 g曲克芦丁粗品,在高于65℃的条件下,溶解到500 mL体积比为27∶1的甲醇与异丙醇的混合溶剂中,撒入三羟乙基芦丁晶种后降温到20~25℃,静置3 h后抽滤晶体,曲克芦丁的含量提高到95%以上,收率不低于75%。     

Optimal operation of enantioseparation by batch-wise preferential crystallization

This article describes batch-wise preferential crystallization separation of mixtures of L- and D-threonine. The use of online polarimetry combined with refractometry and microscopic investigation of the solid phase provides information on the crystallization kinetics. Results obtained for different crystallization conditions (supersaturation, temperature and enantiomeric excess) in a batch crystallizer are presented. Based on these results, a non-linear dynamic model has been developed. The control problem is to determine an optimal temperature profile which will result in a maximum amount of product with required quality. In this dynamic optimization problem B-splines have been used for interpolation of the temperature profile.     

Hybrid separation processes combining vacuum distillation with fractional crystallization,partial melting,and granulation

The physicochemical fundamentals of the combined processes of distillative crystallization (also called distillation crystallization or distillative freezing) and distillative sweating (also called distillation sweating or distillation melting) are considered. Results of the experimental study of the kinetics of separation of binary and ternary organic mixtures of various forms (liquids, powders, continuous layers, and granules) are presented. The high efficiency of the combined processes that make it possible to rapidly decrease the impurity content by one to two orders of magnitude after a single stage is shown. It is found that these processes can be used for effective separation of the mixtures of a eutectic composition when conventional crystallization is not applicable. Dependences of the important kinetic characteristic—an effective diffusion coefficient—on pressure are determined for a number of mixtures. An empirical formula for estimating its values is proposed. It is found that the kinetic features of the combined processes conducted under nonequilibrium conditions can cause both a decrease and an increase in the efficiency of separation of the mixtures of different types in comparison with calculated values for the equilibrium process. A method is developed that makes it possible to combine distillative crystallization with the granulation of a melt in a semicontinuous or continuous process on a cooled movable belt. The method ensures the additional purification of solidifying granules from volatile impurities. Results of calculating the main characteristics of the combined process for purifying naphthalene granules in the batch and continuous modes are given.     

Solve separation units by combining sure and fast models

Problems met in countercurrent separation units have been solved by means of a proper combination of two different models, referred to as sure and fast, to describe the whole set of theoretical stages.The “sure” model is employed for trays showing particular features, or disturbances, i.e. feed trays, partial condensers, reboilers, side cuts, intercoolers, etc. as well as for trays adjacent to the previous ones. This model is written in terms of single theoretical tray equations. The “fast” model is applied to multitray sections, provided that no “disturbance” exists, with an assumption that molar flowrates and temperatures vary according to prefixed laws. The adoption of effective K-values allows one to use formally the same operating equations for the multitray sections as for single theroretical trays.A Newton—Raphson procedure, combined with a B. P. method, is employed to converge the set of equations describing the problem.     

Chiral separation using a novel combination of cooling crystallization and a membrane barrier: Resolution of DL-glutamic acid

Chiral separation of racemic mixtures is essential in the production of many pharmaceutical compounds. The present work describes a novel chiral separation technique that combines cooling crystallization and a membrane separation that is used in DL-glutamic acid resolution. The process utilizes two crystallization chambers that are separated by a membrane that prevents transport of crystals from one chamber to another. Importantly, conditions must be controlled so that only a pure species crystallizes in each of the chambers. This is done by appropriate addition of seed crystals to each chamber and by restricting the formation of new crystals to secondary nucleation mechanisms. The seed crystals may grow or participate in secondary nucleation, but conditions must be controlled so as to prevent primary nucleation, which would result in the formation of both crystal species in each chamber. Experiments were conducted with different amounts of seed crystals to determine operating conditions that produce the high product yield and purity. The results show that this novel chiral separation process is promising: the product purity was over 94% (with a separation factor of 16) and the product yield was increased by as much as 56% more than could be obtained with simple cooling crystallization.     

Separation of rosmarinic acid by facilitated pertraction

Rosmarinic acid has been separated by facilitated pertraction with D2EHPA dissolved in dichloromethane. The pertraction has been carried out in presence of 1-octanol, added into the liquid membrane. The addition of the alcohol led to the increase for more than twice the rosmarinic acid initial and final mass flows, this effect being directly related to the process variables (pH-gradient between the aqueous phases, carrier and alcohol concentrations inside the membrane phase, mixing intensity). But, the influence of 1-octanol on the transport capacity of the pertraction system was negative, its addition inducing the accumulation of rosmarinic into the liquid membrane. Due to this effect, the reevaluation and optimization of the reextraction process from the membrane phase to the stripping are required.     

Numerical solutions of population balance models in preferential crystallization

This article focuses on the implementation of numerical schemes to solve model equations describing preferential crystallization for enantiomers. Two types of numerical methods are proposed for this purpose. The first method uses high resolution finite volume schemes, while the second method is the so-called method of characteristics (MOC). On the one hand, the finite volume schemes which were derived for general system in divergence form are computationally efficient, give desired accuracy on coarse grids, and are robust. On the other hand, the MOC offers a technique which is in general a powerful tool for solving growth processes, has capability to overcome numerical diffusion and dispersion, gives highly resolved solutions, as well as being computationally efficient. Several numerical test examples for a preferential crystallization model with and without fines dissolution under isothermal and non-isothermal conditions are considered. The comparison of the numerical schemes demonstrates clear advantages of the finite volume schemes and the MOC for the current model.     

熔融结晶技术分离纯化有机化合物的研究进展

熔融结晶技术是利用被分离物质各组分间凝固点的差异,通过控制热量的输入和移出,使被分离组分从熔融液中结晶析出,经洗涤、发汗等操作,实现目标组分分离纯化的一种结晶技术。熔融结晶分离纯化技术由于具有不需要使用溶剂、能耗低、设备体积小、能得到高纯产品等优点,在有机化合物的分离纯化领域得到了广泛应用。本文简述了熔融结晶的方式,介绍了熔融结晶器的类型,综述了熔融结晶技术分离纯化有机同分异构体、有机化工原料、日用品、食品和药品的研究进展,分析了熔融结晶技术分离纯化有机化合物过程中存在的问题,展望了熔融结晶技术分离纯化有机化合物的发展方向。文中指出：随着熔融结晶技术的发展,以提高产品质量,减小能耗和降低成本为目的的耦合熔融结晶技术已成为熔融结晶技术发展的方向。以包含熔融结晶设备、工艺、晶体成核和生长动力学、发汗机理以及传热传质模型的系统工程将会成为熔融结晶分离纯化有机化合物的研究热点。     

高效液相色谱手性固定相拆分手性化合物

在纤维素衍生物手性固定相上直接拆分了3种手性化合物,并初步探讨了流动相组分———醇的种类及结构对拆分手性化合物的影响。     

几种手性化合物的液相色谱直接手性拆分

在自行合成的纤维素-三(3,5-二甲基苯基氨基甲酸酯)手性固定相上直接拆分了4种外消旋化合物,初步探讨了手性化合物结构及流动相中的醇在手性识别过程中对手性拆分的影响。     

The separation of glycerides by crystallization in a thermal gradient

Summary An apparatus designed to separate materials by automatic recrystallization in a thermal gradient has been tested for its ability to separate model glyceride mixtures. The theory of the separation has been discussed. The apparatus was able to separate the model mixtures efficiently; the separation was limited only by the actual relative solubilities of the components and the formation of eutectic mixtures. This apparatus should be useful in the separation of many lipide mixtures where crystallization is an appropriate technique. Presented at the fall meeting of the American Oil Chemists' Society, Chicago, Ill., October 20–22, 1958. Journal Paper No. J-3522 of the Iowa Agricultural and Home Economics Experiment Station, Ames. Project 1128. Supported in part by a grant from the American Dairy Association. This paper is based on a thesis presented by Jon R. Magnusson to Iowa State College in partial fulfillment of the requirements for a master's degree.     

溶析结晶法分离莱鲍迪甙A的工艺研究

采用溶析结晶法分离甜菊糖苷中的莱鲍迪甙A(RA),考察溶析剂及其含量、溶液浓度、结晶温度、结晶时间对结晶率和分离系数〔0.87×SRA/(Stotal-SRA)〕的影响。结果表明,在乙酸乙酯含量50%,溶液浓度20 g/L,结晶温度18℃,结晶时间8 h的条件下,结晶率为0.34,分离系数为3.8。     

高效液相色谱法纤维素类手性固定相分离手性化合物

在手性柱OJ-H上直接分离了三种手性化合物,并初步探讨了手性化合物在不同流动相的组分———醇的种类及结构对手性拆分的影响,结果发现,溶质与固定相分子之间的氢键作用、π-π作用对溶质的手性分离有一定的影响。另外,不同直链醇作为流动相也影响着手性化合物的保留与分离。     

Batch crystallization and solid-liquid separation of potassium sulphate

The physical form of potassium sulphate crystals produced in laboratory scale batch crystallizers by both cooling and by precipitation is studied in terms of its subsequent effect on solid-liquid separation characteristics. Control of operating conditions improves the crystal size distribution in both cases and considerably increases the permeability of the precipitates.     

植物生长调节剂多效唑的手性分离

使用直链淀粉衍生物涂敷型手性固定相对植物生长调节剂多效唑对映异构体进行了高效液相色谱手性拆分,正己烷分别添加了乙醇、丙醇、异丙醇、丁醇和异丁醇作为流动相,考察了醇含量对拆分的影响。圆二色(CD)检测器确定了对映体的出峰顺序并测定了圆二色特性。多效唑两对映体在V正己烷∶V异丙醇=95∶5流动相条件下可以实现完全分离,分离度达1.63。230nm波长下,出峰顺序为 /-,波长超过238nm,多效唑两对映体无圆二色吸收。     

溶剂结晶法分离精制豆甾醇工艺对比

通过对溶剂结晶法分离精制豆甾醇工艺进行对比分析,得出工艺简单、适合工业化生产工艺路线。介绍国内外溶剂结晶法（多级分步结晶法、极性溶剂结晶法、有机溶剂结晶法）分离精制豆甾醇的工艺方法并进行对比,可知有机溶剂结晶法中的重结晶法工艺比较简单,非常适合工业化生产。