Integrated Simulated Moving Bed Processes for Production of Single Enantiomers

Based on the assumption of true moving bed processes it was demonstrated that integration of a racemization reaction into a continuous chromatographic process can improve the production of single enantiomers. In view of possible practical implementations, the analysis is extended to more realistic simulated moving bed (SMB) processes. Superstructures of SMB‐based systems are defined that reflect the three general concepts of flow sheet, partial, and total process integration. Process candidates are generated by simultaneously optimizing process structure and operating conditions. Optimal process setups are determined under idealized conditions as a function of the purity requirement. The best performance is achieved by fully integrated processes. These are compared under more realistic conditions to units with side reactors. The results indicate that a simple fully integrated SMB system with three zones is a particularly promising new process option. The new concept is investigated in detail to identify relevant practical aspects.     

Full Superstructure for Multiobjective Optimization of Multicolumn Chromatography for Ternary Separations

In the past decades, many multicolumn chromatographic processes have been proposed and studied for multicomponent continuous separation. In this study, the optimal operation for ternary multicolumn chromatographic separation is obtained from a full superstructure which embeds many different operations. A multiobjective optimization problem was solved to analyze the trade‐off between the throughput and the purity of the target component. It was found that the throughput of the optimal operation found from the full superstructure is significantly higher than that of the generalized full cycle scheme in our former publication in 2012.     

新型多组分连续制备色谱系统--阵列式柱色谱

本文介绍了一种新型多组分连续制备色谱系统———阵列式柱色谱。该系统是在综合了模拟移动床色谱和旋转环状色谱的工作原理的基础上开发出来的 ,主要由控制部分、流体输送部分、分离部分、检测部分和收集部分所组成。在分离部分中 ,本系统用色谱柱阵列代替了旋转环状色谱的环形填料层 ,即避免了溶质横向扩散和动密封问题 ,又可以根据实际生产需要增减色谱柱数目 ;在收集部分中 ,使用了专门为本系统设计的收集器实现了所有色谱柱流出液的集中收集 ;本系统采用将试验和生产一体化的设计 ,通过将单柱模式下的使用在线检测得出的优化分离条件应用到多柱模式中 ,实现了系统的柔性设计 ,降低了设备成本 ;用户可以通过使用装有系统控制软件的上位机与系统进行实时交互 ,大大提高了系统运行自动化程度 ,简化了操作。具有上述优点的本系统必将有着广泛的应用前景     

Dynamics of Simulated Moving-Bed Adsorption Separation Processes

Abstract

Two mathematical models, namely the continuous moving-bed model (steady-state model) and the intermittent moving-bed model (transient model), have been used to describe simulated moving-bed adsorption separation processes. Four-column and 12-column simulated moving-bed systems for the separation of optical isomers with nonlinear adsorption isotherms were studied with the two models, respectively. The model equations were solved by using the numerical method of orthogonal collocation in finite elements. For the 4-column simulated moving bed, the differences between the simulation results from the two mathematical models are very obvious. Process dynamics, i.e., evolution of the species concentrations in the extract and raffinate and the axial profiles at different times, of the above systems in one switching period at the cyclic steady state are presented and discussed. They were numerically simulated with the intermittent moving bed model. The computations in a Cray J916 computer were very time consuming for the 12-column system.     

General optimization strategy of simulated moving bed units through design of experiments and response surface methodologies

The optimization of simulated moving bed (SMB) units is often performed through detailed phenomenological models and require extensive computation time. Hence several optimization methods like the Triangle Theory, and the concept of separation volume have been proposed. However, they do not provide accurate results, when mass transfer limitations are significant, or require a large number of simulations.In this work, a combined Design of Experiments and Response Surface Methodology (DoE-RSM) approach is proposed for SMB optimization, aimed at providing good results with simplicity and reduced number of simulations. The separation of trans-stilbene oxide enantiomers is selected as case study in order to compare DoE-RSM with previous approaches. In the whole, accurate results are obtained with a few number of simulations, allowing for purities above 99.60% for both enantiomers, and productivity of 65.41 kg/(m³_adsorbent day). The versatility of DoE-RSM tool is also discussed, emphasising their advantages and general applicability.     

Chiral Separation of Ketoprofen Enantiomers by Preparative and Simulated Moving Bed Chromatography

The pharmaceutical industry is now directed to the market of more safety and efficient drugs, based on single enantiomers. Ketoprofen, still used as a racemic pharmaceutical drug, belongs to the profens class, one of the most representative of the non-steroidal anti-inflammatory drugs. This work presents the chiral separation of ketoprofen enantiomers by simulated moving bed technology, using a laboratory scale unit (the FlexSMB-LSRE®) with six columns, packed with the Chiralpak AD® stationary phase (20 μm). A comparative study between a mobile phase composed of a traditional high hydrocarbon content (10%ethanol/90%n-hexane/0.01%TFA) and a strong polar organic composition (100%ethanol/0.01%TFA) is presented. The study includes the measurement of the adsorption isotherms, elution, and frontal chromatography experiments, carried out on a SMB column for both compositions. The results obtained allowed the prediction and optimization of the SMB operation. Using pure ethanol as solvent and a racemic feed concentration of 40 g/L, purities above 98.6% on both outlet streams were obtained, with a productivity of 3.84 g_feed/(L_bed.hr) and a solvent consumption of 0.78 L_solvent/g_feed. The results obtained in the experimental separation of ketoprofen enantiomers by SMB chromatography indicates that pure ethanol presents better performances than the classic high hydrocarbon content composition.     

模拟移动床在对二甲苯生产中的应用

介绍了工业生产对二甲苯（PX）的吸附分离工艺原理,并阐述了利用计算机控制模拟移动床技术生产对二甲苯的方法。     

Hybrid Process for o‐ and p‐Xylene Production in Aromatics Plants

A new hybrid process for the production of o‐ and p‐xylene is proposed to replace the traditional plant of aromatics in refineries. The proposed process comprises a simulated moving bed (SMB) unit and two crystallizers. The SMB technology as the first unit of the suggested process is applied for the separation of xylene isomers and was investigated by simulation of an industrial size unit, using experimentally measured adsorption equilibrium data on MIL‐53(Al)‐shaped material. The separation of p‐xylene from o‐xylene with m‐xylene as desorbent is the key characteristic of this method. An industrial‐scale SMB unit could provide extract and raffinate streams with very high purities.     

Separation of amino acids by simulated moving bed under solvent constrained conditions for the integration of continuous chromatography and biotransformation

A large number of promising enzyme reactions, such as diastereospecific carbon-carbon bond formation by aldolases, suffers from an unfavorable position of the reaction equilibrium. Combining continuous chromatography and enzymatic reactions should allow for a new in situ or online product recovery process to achieve high reaction productivity and yield and make these biocatalysts economically more attractive. The integration imposes a series of constraints on the chromatographic separation, mainly on the applicable solvent, which is at the same time the reaction medium for the enzymatic reaction. We exploit this concept for a model process, the integrated biocatalytic production of L-allo-threonine from glycine and acetaldehyde. Of crucial importance for this process is the separation of the two physicochemically similar amino acids glycine and threonine, in particular in the presence of additional compounds such as the second starting material and enzyme cofactors. This separation was first investigated on a lab-scale simulated moving bed (SMB) unit under enzyme compatible conditions. After triangle theory-based identification of SMB operating points, the two amino acids could be efficiently separated, applying aqueous eluents with minor content of organic co-solvent at neutral pH on a weak cation exchanger resin. Remarkably, the separation performance with respect to the two amino acids was only slightly reduced by coupling the SMB to a continuously operated enzyme membrane reactor, whose efflux contained, in addition to the amino acids, acetaldehyde and the cofactor pyridoxal-5-phosphate. This represents an important step to the future design of even further integrated biocatalytic reaction-separation schemes.     

Separation of Ternary Mixtures by Pseudo‐Simulated Moving‐Bed Chromatography: Separation Region Analysis

The application of the pseudo‐simulated moving bed process, known as JO process of Japan Organo Co., to the separation of ternary mixtures was studied. In order to perform a desired separation, the choice of the different operation parameters such as the duration of each step and its respective flow rates requires the use of a methodology that could provide the best process performance. This issue is addressed by proposing an innovative method to determine the JO operation region, which establishes the operation limits of the process. In addition, a methodology is presented to determine the separation region where a minimum purity requirement is guaranteed. This methodology was applied to a ternary mixture considering linear adsorption isotherms. It was possible to construct a separation region for minimum purity of 99.9 % in all the outlet streams and identify the best operation point in terms of the process performance.     

Operation Strategies for Simulated Moving Bed in the Presence of Adsorbent Ageing

Abstract

The effect of adsorbent ageing on the operation of Simulated Moving Bed (SMB) units is addressed, for two different systems (linear and non‐linear isotherms). Two different consequences of adsorbent deactivation are considered, one involving the loss of adsorption equilibrium capacity and the other related to the increase of mass transfer resistance. For each of these cases one direct and straightforward compensation measure is presented: the increase of the solid velocity (decrease of switching time) to compensate the adsorbent capacity decline and the decrease of solid and internal flow rates to compensate the mass transfer resistances increase. It is possible to compensate the adsorbent capacity decline, maintaining all SMB performance parameters, limited to the reduced contact time when high solid velocities are used. In the second case, when mass transfer resistance increases, it has been shown that the direct compensation strategy would lead to a decrease of productivity, to keep the same purity and recovery as with fresh adsorbent.

Another possible corrective method to the ageing problem is the use of variable switching times in the non‐conventional “modus operandi”‐Varicol, a sort of re‐arrangement of the SMB columns distribution by sections, here tested for the case of adsorbent capacity decline case as a consequence of adsorbent ageing mechanisms.     

Comparison between the Reverse‐Flow Reactor and a Network of Reactors for the Oxidation of Lean VOC Mixtures

Catalytic reactors in forced nonstationary operation enable autothermal VOC (volatile organic compounds) oxidation even when the adiabatic temperature rise of the combustible mixtures is extremely low. The simulated moving bed (or ring reactor), realized with a network of two or three reactors, has been suggested as an alternative to the well‐investigated reverse‐flow reactor. The behavior of these configurations has been compared, showing that the reactor network has a narrower stability range than the reverse‐flow reactor; the stability range is decreased if we increase the number of reactors. The maximum temperature of the catalyst is higher in the network than in the reverse‐flow reactor and in both configurations it is increased if part of the catalyst is substituted by inert material.     

An Adaptive Control Concept for Simulated Moving Bed Plants in Case of Complete Separation

Simulated Moving Bed (SMB) technology has played an important role in the separation of binary mixtures. An exact adjustment of the volumetric flow rates is necessary for trouble‐free operation. In this contribution, an adaptive control concept is introduced that determines the necessary control variables for complete automatic separation. A simple model is derived for the movement of the concentration fronts and a controller is developed based on the model. The simulation result shows the potential of applying such a control design for application in industrial use.     

模拟移动床色谱生产精品茄尼醇的原料预处理工艺研究

比较了茄尼醇提取物粗提纯方法;采用液相制备色谱法进行粗提纯。条件固定相为水型ODS;流动相为乙醇和水混合液;洗脱方式为梯度洗脱,先用V(乙醇)∶V(水)=20∶80流动相冲洗1500 mL,再用V(乙醇)∶V(水)=5∶5冲洗4000 mL;最后1000 mL用纯甲醇冲洗柱子。V(乙醇)∶V(水)=5∶5冲洗馏分段为产品段。产品液用薄膜旋转蒸发器在60℃浓缩。     

Continuous prediction technique for fast determination of cyclic steady state in simulated moving bed process

In the simulation of cyclic processes, such as simulated moving bed (SMB), the system should be equilibrated to reach a cyclic steady state (CSS) before evaluating the process performance. However, the conventional method of successive substitution is quite time-consuming. In this work, a continuous predicting method (CPM) is developed for fast determination of CSS in SMB. In CPM, the direct prediction of state variable at CSS and solving model equation are conducted alternately until CSS is reached. In order to give a guideline for the selection of the acceleration factor, CPM is applied on SMB process for enantioseparation of 1,1′-bi-2-naphtol racemate and with the optimized acceleration factor, 59% of computation time saved compared with successive substitution. In addition, this method is further successfully used in a sugar separation process. Given its efficiency and simplicity, this method could provide a useful tool for SMB simulations.     

模拟移动床色谱手性分离过程的非线性非理想模型

A non-linear non-ideal model,taking into account non-linear competitive isotherms,axial disperison,film mass transfer,intraparticle diffusion,and port periodic switching,was developed to simulate the dynamics of simulated moving bed chromatography(SMBC),The model equations were solved by a new efficient numerical technique of orthogonal collocation on finite elements with periodical movement of conceantration vector,The simulated SMBC performance is in accordance with the experimental results reported in the literature for separation of 1,1‘‘‘‘‘‘‘‘-bi-2-naphtol enantiomers using SMBC,This model is useful for design,operation ,optimization and scale-up of non-linear SMBC for chiral separations with significant non-ideal effects,especially for high solute concentration and small intraparticle diffusion coefficient or large chiral stationary phase particle.     

Analysis and demonstration of a control concept for a heat integrated simulated moving bed reactor

Successful operation of a simulated moving bed reactor requires a strategy to control switching of the inlet and outlet positions between different fixed-bed segments. This is due to the narrow operation window in which an ignited state can be maintained and complete conversion is assured in exothermal irreversible reactions. This work compares three control concepts, which are either based on monitoring the reaction front or the leading thermal front. Another feature investigated is the length of the observation time considering a single switching period and a complete cycle. For the concept favored some efforts regarding parameterization are made. The wider range of temperature set-points applicable can be related to stability limits of an associated hypothetical true moving bed reactor. Responses to step inputs in feed concentration and total flow rate are investigated experimentally in order to evaluate the performance of the controller suggested. An ignited state of the reactor could be maintained successfully for 3.5 days.     

SMB两组份色谱分离过程建模与优化

基于TMB建模方法建立了二组份SMB色谱分离过程的理想数学模型。以提高产品纯度和收率为目标,依据Massimo三角形理论,研究了主要操作参数对SMB性能的影响,针对具体的分离对象进行了操作条件寻优仿真,并以此指导实际分离实验,得到满意的结果。     

模拟移动床色谱拆分D-塔格糖和D-半乳糖的模拟研究

模拟移动床色谱操作参数的模拟和优化对实际分离生产具有重要的指导意义。本文采用平衡扩散模型,对模拟移动床色谱分离D-塔格糖和D-半乳糖进行了模拟研究,根据三角形理论确定了其最佳操作参数,并考察了各区柱数配置、切换时间和分离区流量等变化对分离效果的影响,验证了模拟移动床操作参数的敏感性和模型建立的必要性。