Abel Stefanie, Mazzotti Marco, Morbidelli Massimo
ETH Zürich, Institut für Verfahrenstechnik, Switzerland.
J Chromatogr A. 2002 Jan 25;944(1-2):23-39. doi: 10.1016/s0021-9673(01)01087-1.
The simulated moving bed (SMB) is a multi-column chromatographic separation process, which--with respect to the single-column preparative batch process--allows for a continuous separation with larger productivity and smaller solvent consumption at the same time. The benefits of this process have been shown for several different applications in fine chemistry, particularly for the separation of enantiomers. In general, SMBs are operated under isocratic conditions. However, separation performance can be further improved by applying some sort of gradient mode operation, in order to optimize the operating conditions of each individual section of the unit. This can be achieved by tuning the retention behavior of the solutes to be separated along the unit, namely by enforcing weak adsorption conditions in sections 1 and 2, and strong adsorption conditions in sections 3 and 4. This can be achieved by applying a temperature gradient (high temperature in section 1, and low temperature in section 4), a pressure gradient (e.g. in the supercritical SMB, when pressure is high in section 1, and low in section 4), or a solvent gradient, which is the aim of this work. In the solvent gradient mode the mobile phase consists of a mixture of two or more solvents. To different mobile phase compositions corresponds a different retention behavior of the solutes, i.e. different adsorption isotherms. In this work we study a closed loop SMB unit with solvent mixtures of two different compositions entering the unit at the feed and desorbent inlet ports, respectively. Thereby two different mobile phase compositions are established in sections 1 and 2, and sections 3 and 4, respectively. To optimize this process the equilibrium theory design criteria for non-linear SMBs are extended to describe this operation mode. It is shown how the region of separation is derived and how the optimal operating conditions can be found. Finally the solvent gradient mode is compared with the isocratic mode in terms of productivity and solvent consumption.
模拟移动床（SMB）是一种多柱色谱分离过程，相对于单柱制备间歇过程，它能够实现连续分离，同时具有更高的生产率和更低的溶剂消耗。该过程的优势已在精细化学的多种不同应用中得到体现，特别是在手性异构体的分离方面。一般来说，SMB在等度条件下运行。然而，通过采用某种梯度模式操作，可以进一步提高分离性能，以便优化装置各部分的操作条件。这可以通过调节沿装置长度方向待分离溶质的保留行为来实现，即在第1和第2段采用弱吸附条件，在第3和第4段采用强吸附条件。这可以通过施加温度梯度（第1段高温，第4段低温）、压力梯度（例如在超临界SMB中，第1段压力高，第4段压力低）或溶剂梯度来实现，而这正是本研究的目标。在溶剂梯度模式下，流动相由两种或更多种溶剂的混合物组成。不同的流动相组成对应着溶质不同的保留行为，即不同的吸附等温线。在本研究中，我们考察了一个闭环SMB装置，两种不同组成的溶剂混合物分别从进料口和解吸剂入口进入装置。由此，在第1和第2段以及第3和第4段分别建立了两种不同的流动相组成。为了优化该过程，将非线性SMB的平衡理论设计准则进行扩展，以描述这种操作模式。展示了如何推导分离区域以及如何找到最佳操作条件。最后，在生产率和溶剂消耗方面，将溶剂梯度模式与等度模式进行了比较。
