Absence of experimental evidence of a delta-shock in the system phenetole and 4-tert-butylphenol on Zorbax 300SB-C18.

We investigate the system consisting of phenetole (PNT) and 4-tert-butylphenol (TBP) in methanol-water (63:37 v:v) on a Zorbax 300SB-C18 column by characterising single component isotherms, by performing a large number of binary experiments of different types and by describing the experiments through simulations carried out using a novel, rather powerful competitive adsorption isotherm, that we call the generalized bi-Langmuir isotherm. This system is of great interest because it was previously reported to yield a new type of transition in nonlinear chromatography, the so-called delta-shock. Such transition had been discovered earlier through a theoretical analysis and confirmed by detailed simulations. The initial aim of this work was to reach a satisfactory agreement between delta-shock experiments and corresponding numerical simulations. In the course of this work however, a number of inconsistencies in the interpretation of the previous experimental results were highlighted and explained. This led to a new experimental campaign, which is reported here and has allowed to reach two important conclusions: (1) The binary system PNT-TBP mentioned above does not exhibit a delta-shock; the spike in the UV profile, which has previously been interpreted as an experimental evidence of the delta-shock, results from liquid-liquid phase separation within the chromatographic column. (2) The same system exhibits a rather peculiar behavior in breakthrough and displacement experiments, which could be well described using the generalized bi-Langmuir isotherm.

Three column intermittent simulated moving bed chromatography: 3. Cascade operation for center-cut separations.

A general design methodology for chromatographic three fraction separation by application of the three column intermittent simulated moving bed (3C-ISMB) cascade is proposed and experimentally validated by studying the purification of an intermediately retained stereoisomer of nadolol, from an equimolar mixture of its four stereoisomers. The theoretical part shows that the 3C-ISMB cascade can be easily designed by applying Triangle Theory. Moreover, a re-scaling approach for the second stage is proposed so as to account for the fact that the feed flow rates to stage 2 are generally higher as compared to stage 1 due to dilution in the latter. Scaling the columns of the second stage accordingly enables to run both stages under optimal conditions with respect to switching time and step ratio, which is an important advantage as compared to integrated ternary processes. The experimental part starts with studying the linear adsorption behavior of nadolol in heptane/ethanol/DEA on Chiralpak AD for varying ratios of heptane and ethanol. Based on that, a solvent composition of Hept/EtOH/DEA 30/70/0.3 (v/v/v) is selected and the competitive multi-component Langmuir isotherm of the quaternary mixture is determined by frontal analysis. The resulting isotherm parameters are used to design several first stage experiments aiming at removal of the most retained component. The resulting ternary intermediate product is reprocessed in several second stage experiments studying various configurations. Finally, the dilution of the intermediate product with Hept/DEA yielding a solvent composition of Hept/EtOH/DEA 60/40/0.3 (v/v/v) is examined showing that the resulting increase in retention is beneficial for final product purities. Moreover, the reduction in viscosity compensates for the dilution as it enables higher flow rates. Dilution of the intermediate product is hence the best option, yielding highest overall cascade productivity (2.10gl(-1)h(-1)) and highest product purity (97.8%) requiring a specific solvent consumption of 12l/g of product.

Three-column intermittent simulated moving bed chromatography: 2. Experimental implementation for the separation of Tröger's Base.

The three-column intermittent simulated moving bed (3C-ISMB) process has been presented in the first part of this series [1]. A theoretical comparative analysis of the new process to intermittent simulated moving bed (I-SMB) demonstrated successfully the potential of the 3C-ISMB technology. Particularly, 3C-ISMB was shown to substantially outperform I-SMB in terms of productivity whilst maintaining high purity specifications and without significantly sacrificing solvent consumption. Moreover, we demonstrated the applicability of Triangle Theory for 3C-ISMB design, which is an important advantage compared to other modified SMB schemes. In the present work we report on the experimental implementation of the 3C-ISMB technology demonstrating the simplicity of retrofitting an existing SMB or I-SMB plant. Moreover, we perform an experimental comparative analysis studying the well-known separation of Tröger's Base enantiomers in pure ethanol on Chiralpak AD™. In a comprehensive series of experimental runs, each examining three different modes of operation, applying total feed concentrations ranging from 5 g/l to 17.4 g/l, we assess and compare the separation performances of both conventional I-SMB and 3C-ISMB. This series of experiments successfully demonstrates that 3C-ISMB delivers the same high purity levels as conventional I-SMB whilst significantly outperforming the conventional process in terms of productivity; in fact an increase of more than 80% is achieved.

Three column intermittent simulated moving bed chromatography: 1. Process description and comparative assessment.

The three column intermittent simulated moving bed (3C-ISMB) process is a new type of multi-column chromatographic process for binary separations and can be regarded as a modification of the I-SMB process commercialized by Nippon Rensui Corporation. In contrast to conventional I-SMB, this enables the use of only three instead of four columns without compromising product purity and throughput. The novel mode of operation is characterized by intermittent feeding and product withdrawal as well as by partial recycling of the weakly retained component from section III to section I. Due to the smaller number of columns with respect to conventional I-SMB, higher internal flow rates can be applied without violating pressure drop constraints. Therefore, the application of 3C-ISMB allows for a higher throughput whilst using a smaller number of columns. As a result, we expect that the productivity given in terms of throughput per unit time and unit volume of stationary phase can be significantly increased. In this contribution, we describe the new process concept in detail and analyze its cyclic steady state behavior through an extensive simulation study. The latter shows that 3C-ISMB can be easily designed by Triangle Theory even under highly non-linear conditions. The simple process design is an important advantage to other advanced SMB-like processes. Moreover, the simulation study demonstrates the superior performance of 3C-ISMB, namely productivity increases by roughly 60% with respect to conventional I-SMB without significantly sacrificing solvent consumption.