Seeding reactive crystallization

In some cases, a crystallization procedure is unsatisfactory for producing satisfactory seed crystals for subsequent use. This is particularly true for reactive crystallization because of the fine particles normally produced by this method. Since no amount of fine particle seed is satisfactory for significant growth in succeeding batches, the next possibility is to increase the particle size of the seed. To accomplish this, it is necessary to grow seeds in a separate operation from the reactive crystaUization. Other applications may also require separate preparation of grown seed. The foUowing procedure is one possible method. 

The needles shown in Fig. 10-3a were subjected to this heat-cool treatment resulting in the large three-dimensional crystals shown in Fig. 10-3b. Success in growing seed crystals both prepares seed for larger batches and establishes that this compound will actuaUy grow. It is then necessary to determine if it will grow at a practical rate in the actual reactive crystallization system. 

The most effective seeding is achieved in semicontinuous and continuous crystallizations by the nature of the operations themselves, in which the seed is always present and in large quantity. Although common in large industrial operations, these techniques have found more limited application in the pharmaceutical industry. Exceptions to this are detailed in Examples 7-6 and 11-6, on the continuous resolution of optical isomers in fluid bed crystal-fizers, and in Example 10-1, which presents a semicontinuous method of utilizing seed heel recycle in reactive crystallization to achieve primarily growth. 

Figure 10-1 Schematic representation of addition modes for reagents in reactive crystallization the relationship between the amount of reagent added and the metastable region with and without seed.

The number, surface area, and surface condition of seed crystals are critical to successful minimization of nucleation and realization of growth. (Seeding issues are also discussed in Chapter 5, and only those issues of primary consideration in reactive crystallization are discussed here.)... 

The requirement for increased amounts of seed for reactive crystallization compared with the cooling, evaporahon, and anti-solvent methods is discussed by Mullin (2001, p. 339). Amounts of seed up to 50% are indicated to be necessary in recycle systems to provide the seed area necessary. The requirement for this increased amount is the direct result of the rapid development of supersaturation by reaction and the need to have sufficient surface area for growth throughout the operation, especially at the start of reagent addihon. 

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,... 

Since no amount of fine needle seed is satisfactory, the next possibility is to increase the particle size of the seed. To accomplish this, it is necessary to grow seeds in a separate operation from the reactive crystallization. 

As with any crystallization process, reactive crystallization will, in general, produce fine particles unless the entire operation is run within the metastable region. This condition can be realized by provision of heavy seeding and by slow addition to control supersaturation at a low level. Adequate mixing is necessai-y, but shear damage must be avoided by selection of the correct impeller speed and type. 

This example is another illustration of the important effects of seeding and addition rate on reactive crystallization. In the example, the filtration rate of the product crystals is used as a measure of the impact of these critical variables. 

Resolution Crystal growth in this reactive crystallization can be controlled by limiting supersaturation by slow reagent addition, high level seeding, and low-shear, high-circulation mixing. 

It has been presented here that there is not a unique Ti-Beta material, but the characteristics and catalytic performance strongly depend on chemical composition and synthesis procedure. Then, new synthesis procedures which allow to prepare samples with much lower A1 content than any one reported before have been developed. Moreover, by using highly reactive and stable seeds, crystals of Ti-Beta zeolite have been produced, which have an inner core of aluminosilicate composition, covered by an outer shell of Titanosilicate which accounts for about 98 % of the mass. These synthesis methods have lead to samples which present an improved catalytic behaviour for reactions such as olefin oxidation and phenol hydroxylation using H202 as oxidant. 

The polymerization of the white phosphorus to the initially still reactive light red phosphorus takes place at 280° under rapid rotation of the ampul, so that the seed crystals are dispersed in the molten white phosphorus and an intimate mixture of red phosphorus, seed crystals, and metallic mercury results. After 3 days, the temperature is raised to 360° for one day and then maintained at 380° for 3 days. The rate of the rotation of the tube may now be reduced since its contents have become solid. After cooling, the tube can be opened. A fine film of impure red phosphorus which is observed occasionally on the surface of the black phosphorus can be blown off easily. The black phosphorus... 

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