Crystallization process synthesis

Keywords Crystallization, Process synthesis, Task based design. Process optimization. 

It is often important to control the CSD of pharmaceutical compounds, eg, in the synthesis of human insulin, which is made by recombinant DNA techniques (1). The most favored size distribution is one that is monodisperse, ie, all crystals are of the same size, so that the rate at which the crystals dissolve and are taken up by the body is known and reproducible. Such uniformity can be achieved by screening or otherwise separating the desired size from a broader distribution or by devising a crystallization process that will produce insulin in the desired form. The latter of these options is preferable, and considerable effort has been expended in that regard. 

Thus, methods are now becoming available such that process systems can be designed to manufacture crystal products of desired chemical and physical properties and characteristics under optimal conditions. In this chapter, the essential features of methods for the analysis of particulate crystal formation and subsequent solid-liquid separation operations discussed in Chapters 3 and 4 will be recapitulated. The interaction between crystallization and downstream processing will be illustrated by practical examples and problems highlighted. Procedures for industrial crystallization process analysis, synthesis and optimization will then be considered and aspects of process simulation, control and sustainable manufacture reviewed. 

As mentioned above, the solids process synthesis approach (Rossiter and Douglas, 1986) has been applied to the optimization of a continuous salt crystallization plant similar to that depicted in Figure 9.2 (Rossiter, 1986). In... 

Berry, D.A. and Ng, K.M., 1997. Synthesis of reactive crystallization processes. American Institute of Chemical Engineers Journal, 43, 1737. 

That benzene hexachloride isomer mixture is then the raw material for lindane production. The production of lindane per se is not a chemical synthesis operation but a physical separation process. It is possible to influence the gamma isomer content of benzene hexachloride to an extent during the synthesis process. Basically, however, one is faced with the problem of separating a 99%-plus purity gamma isomer from a crude product containing perhaps 12 to 15% of the gamma isomer. The separation and concentration process is done by a carefully controlled solvent extraction and crystallization process. One such process is described by R.D. Donaldson et al. Another description of hexachlorocyclohexane isomer separation is given by R.H. Kimball. 

The presence of triethylenetetramine in the hydrothermal synthesis of open-framework zinc phosphates results in a number of frameworks with one- to three-dimensional structures. The structures include one-dimensional ladders, two-dimensional layer structures, and one structure where the tetramine is bound to the zinc center. The structural type was highly sensitive to the relative concentration of the amine and phosphoric acid.411 Piperazine and 2-methylpiperazine can be used as templating molecules in solvothermal syntheses of zinc phosphates. The crystallization processes of the zinc compounds were investigated by real time in situ measurements of synchrotron X-ray powder diffraction patterns.412... 

Zeolites are formed by crystallization at temperatures between 80 and 200 °C from aqueous alkaline solutions of silica and alumina gels in a process referred to as hydrothermal synthesis.15,19 A considerable amount is known about the mechanism of the crystallization process, however, no rational procedure, similar to organic synthetic procedures, to make a specifically designed zeolite topology is available. The products obtained are sensitive functions of the reaction conditions (composition of gel, reaction time, order of mixing, gel aging, etc.) and are kinetically controlled. Nevertheless, reproducible procedures have been devised to make bulk quantities of zeolites. Procedures for post-synthetic modifications have also been described.20 22... 

Heat-up rate effects have been investigated with respect to microwave synthesis of AlPO phases, however there are few publications concerning the heat-up effects in conventional heating [58]. There has also been at least one study of pH and H2O level on aluminophosphate crystallization [59]. A recent paper attempts to study the unique crystallization process of several aluminophosphate molecular sieve compositions [60]. 

X-Ray powder diffraction is a powerful tool for characterization of zeolites. The basic experiment is relatively easy to perform and can be done in most labs on standard diffractometers and the data obtained is easy to analyze for many applications. Powder diffraction can be used to determine whether a new zeolite has been synthesized, whether a desired zeolite has been made or whether a crystallization process has completed. As noted in Section 4.2, X-ray powder diffraction can be an integral tool in determining the details of the structure of a newly synthesized zeolite. In addition, it is a critical characterization technique that can be routinely used, for example, to identify contaminants present in a synthesis, to determine how much zeolite has been bound into a catalyst or adsorbent pellet, or to ascertain if heat treatment alters the zeolite structure. Of the techniques described in this chapter, powder diffraction is probably the most commonly used. Additional details can be found elsewhere [15-19]. 

Some natural polymers such as cotton, slik, and cellulose have the extended-chain morphology, but their morphologies are determined by enzymatically controlled synthesis and crystallization processes. Extended-chain morphology is obtained in some synthetic... 

In our initial paper on the synthesis of VPI-5, we described preparation methods that involved the use of TBA and DPA (ref. 4). Subsequently, we studied further aspects of the crystallization process using a VPI-5 gel (ref. 5) which contained TBA. The results from these experiments lead to the following description for a TBA mediated crystallization of VPI-5. When the... 

The three most interesting routes identified between 1990 and 1995 are compared in Table 12.2 in terms of manufacturing costs, investment, environmental impact, and complexity. Although chiral chromatography is relatively complex compared to diastereomeric salt crystallization or synthesis from a chiral precursor, these figures are clearly in favor of the MCC process, mainly because of manufacturing costs and environmental impact. 

This study showed that the overall crystallization processes for mor-denite, zeolite X, and zeolite A were similar. However, the physical properties of the crystallizing system determine the rate-limiting step for a particular zeolite synthesis. In the case of mordenite in which both the viscosity of the batch composition and the morphology of seed crystals were varied, it was observed that diffusion in the liquid phase was the ratedetermining step. For zeolite X the actual growth rate on the crystal-liquid interface was the rate-limiting factor as shown by identical conversion rates for the seeded and unseeded systems. For zeolite A in the system chosen, both processes influenced the conversion rate. 

Substitution of silicon by other atoms like Ti or Al was reported to improve the thermal and hydrothermal stability to some extent [6]. It was also reported that improved hydrothermal stability could be achieved by adjusting the gel pH several times during crystallization process [7], Post-synthesis silylation technique has also been reported to enhance the hydrothermal stability of mesoporous materials by increasing the hydrophobicity of the samples [8,9]. However, it is most desirable to develop a method for preparing hydrother-mally stable mesoporous material by direct synthesis route. 

Figure 4.4 shows the crystallinity of the TS-1 and silicalite-1 samples synthesized under different conditions in the YNU and method A systems (the Si/Ti ratio in the synthesis gel was 50 for both series of samples). Clearly, the crystallization rate of TS-1 was much slower in the YNU system than that in the method A system and the presence of Ti in the gel not only severely retarded the crystallization process by prolonging the induction period but also reduced the crystallinity of most of the samples. Nevertheless, higher crystallinity of TS-1 was finally achieved in the YNU system than in the method A system. 

---