Large scale separations

Hafnium Carbide. The need of pure zirconium [7440-67-7] for nuclear reactors prompted the large-scale separation of hafnium [7440-58-6] from zirconium. This in turn made sufficient quantities of hafnium dioxide [12055-23-17, Hf02, or Hf metal sponge available for production of HfC for use in cemented carbides (see Hafniumand hafnium compounds). 

Supercritical fluid chromatography (SFC) refers to the use of mobile phases at temperatures and pressures above the critical point (supercritical) or just below (sub-critical). SFC shows several features that can be advantageous for its application to large-scale separations [132-135]. One of the most interesting properties of this technique is the low viscosity of the solvents used that, combined with high diffusion coefficients for solutes, leads to a higher efficiency and a shorter analysis time than in HPLC. 

In general, high selectivities can be obtained in liquid membrane systems. However, one disadvantage of this technique is that the enantiomer ratio in the permeate decreases rapidly when the feed stream is depleted in one enantiomer. Racemization of the feed would be an approach to tackle this problem or, alternatively, using a system containing the two opposite selectors, so that the feed stream remains virtually racemic [21]. Another potential drawback of supported enantioselective liquid membranes is the application on an industrial scale. Often a complex multistage process is required in order to achieve the desired purity of the product. This leads to a relatively complicated flow scheme and expensive process equipment for large-scale separations. 

Resin consumption is low because of the highly efficient use of the capacity of the resin for the enantiomer during each cycle, as well as the material stability of the resin. The above benefits of the ChiraLig M technology result in improved economics for the large-scale separation. 

The interests of SMB for performing large-scale separations of enantiopure drugs has been recognized (very short development time, extremely high probability of success, and attractive purification cost) [68]. Several pharmaceutical and fine chemical companies have already developed SMB processes. However, because of strong confidentiality constraints, public information is limited, and some of the major announcements are summarized below ... 

In preparative chromatography, selectivity and efficiency no longer have the same importance they do in analytical chromatography. A certain selectivity is required in preparative chromatography as everywhere else in order to achieve the separation, but other parameters are at least as important if not more so. These include the loading capacity of the stationary phase and the maximum speed (throughput) of the process. The three main economic criteria for a large scale separation process are... 

Both GC and LC may be operated in one of several modes. The principal modes currently used for large-scale separations are elution, selective adsorption or desorption, and simulated countercurrent chromatography. In addition, reaction and separation can be combined in a single column with unique advantages. Elution is the most used and best developed form of the technique and is described first. 

The principal types of chromatography involved in large-scale separations are summarised in Table 19.2, and some explanatory comments are pertinent. 

Table 19.2. Main types of chromatography for large-scale separation... 

The three main modes of chromatographic operation are elution chromatography, selective adsorption/desorption, and simulated countercurrent chromatography. Of these, elution chromatography, used as a cyclic batch process, was the first to be developed for large-scale separations. 

The almost simultaneous discovery of vinblastine (1) by Noble et al. (57) and by Svoboda and co-workers (58) is one of the the most publicized events in alkaloid chemistry. Since its initial discovery, vinblastine (1) has been reisolated from C. roseus several times (47 9,57-60,) and it has also obtained from C. ovalis (32), C. longifolius (33), and C. trichophyllus (60). The large-scale separation of vinblastine (1) and vincristine (2) from C. roseus received attention from pharmaceutical industries, and several procedures for the separation of these alkaloids have been reported in the patent literature (61-71). 

The most important solid-phase separation materials for column-based separations in modern radioanalytical chemistry are extraction chromatographic materials, and these have been particularly important in automated radioanalytical chemistry. Solid-phase extraction materials based on the covalent attachment of ligands to solid supports also exist, and they have found application in large-scale separation processes for waste or effluent treatment.22 25 They have been commercialized as Analig or SuperLig materials by IBC Advanced Technologies (American Fork, UT). However, they are less well characterized or used for small-column analytical separations. 

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