Development of Reactive Crystallization Processes

Christianto Wibowo, Vaibhav V. Kelkar, Ketan D. Samant, 

This chapter describes in a step-by-step manner a generic strategy that we have been using for the development of various industrial processes. The chapter begins with a discussion of the overall workflow for process development, followed by a description of the way in which a process is synthesized, which relies heavily on the use of phase diagrams. The deviation from equilibrium behavior is accounted for using a model-based approach. This is illustrated with an example on the asymmetric transformation of an enantiomer. 

The very nature of process development necessitates the contributions of all members of a typical development team. Thus, reaction engineers determine reaction kinetics and select the best reactor type, while filtration experts measure the filter cake resistance and washing efficiency. To reduce development time, it is crucial that all of these activities be performed in a coordinated manner. Proper workflow automates such a development process, in whole or part, during which documents, information, or tasks are passed from one participant to another for action, according to a set of procedural rules. 

Integrated Chemical Processes. Edited by K. Sundmacher, A. Kienle and A. Seidel-Morgenstern 

Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30831-8 

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Development of Reactive Crystallization Processes Solid phase... 

For the treatment of electron correlation, Cizek uses classical techniques as well as techniques based on mathematical methods of quantum field theory, namely, a coupled-cluster approach. A rapid development and deployment of these methods during the past decade was stimulated by the realization of the importance of size consistency or size extensivity in the studies of reactive chemical processes. Although truly remarkable accuracy and development have been achieved for ground states of closed-shell systems, an extension to quasidegenerate and general open-shell systems is most challenging. Cizek also works on the exploitation of these approaches to study the electronic structure of extended systems (molecular crystals, polymers107). His many interests in-... 

Fig. 11.1. Overall workflow for the development of a reactive crystallization process.

Several investigators have developed models for the effectiveness of collisions that lead to agglomeration including Nyvlt et al. (1985) and Sohnel and Garside (1992). This complex interaction of hydrodynamics and crystallization physical chemistry is difficult to predict or describe but can be critical to the successful operation and scale-up of a crystallization process. In particular, for reactive crystallization in which high supersaturation levels are inherently present, agglomeration is very likely to occur as the precipitate forms. Careful control may be necessary to avoid extensive agglomeration, as outlined in Section 5.4.3. below and in Examples 10-1 and 10-2 for reactive crystallization. 

The complex issues regarding low solubi I ity and the nucleation characteristics of induction time and nucleation rate must be minimized by the maintenance of low supersaturation so that growth can predominate. Methods for promoting this balance will be indicated. Prior to that discussion, the issues encountered in the development of a reactive crystallization process will be briefly reviewed. 

Development and scale-up of reactive crystallization/precipitation processes can present some of the most difficult challenges in the field. The reader is referred to the quotation in Section 10.1.2 above as a reminder of this difficulty. 

However, the authors have participated in development and scale-up of some successfiil reactive crystallization processes, and the examples to follow (Examples 10-1 and 10-2) are included to illustrate the concepts and application of the principles discussed above in these processes. These developments were based on the three essential concepts of seeding, control of supersaturation and promotion of growth, as described above. The key variables are, therefore,... 

Despite this progress several areas require further development. For example, we have evidenced that only a limited number of force fields are presently available for treatment of ionic salts, It will be very beneficial that this gap will be filled and general, transferable sets of force fields for different classes of ionic systems will be available as is the case with other classes of energetic materials such as nitramines systems. We have also pointed out in this chapter that current classical force fields developed for ionic crystals are limited to description of nonreactive processes. Development of reactive force fields such as reactive empirical bond order potentials for the case of ionic systems will represent a major forward step for simulation of reactions and of combustion and denotation processes. 

Modelling non-isothermal crystallization is the next important step in a quantitative description of reactive processing. This is particularly important, because crystallization determines the properties of the end product. Therefore, the development the spatial distribution of crystallinity, a, and temperature, T, with time throughout the volume of the reactive medium must be calculated. It is also noteworthy that crystallization and polymerization processes may occur simultaneously. This happens when polymerization proceeds at temperatures below the melting point of the newly formed polymer. A typical example of this phenomenon is anionic-activated polymerization of e-caprolactam, which takes place below the melting temperature of polycaproamide. 

Modelling of crystallization was discussed in Section 2.8. Now, we shall develop a model for superimposed polymerization and crystallization processes. This model is important for calculating temperature evolution during reactive processing, because an increase in temperature, regardless of its cause, influences the kinetics of both polymerization and crystallization. This concept is expressed by the following equation for the rate of heat output from the superimposed proceses 102,103... 

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