Preferential crystallization, production

Figure 11.2 shows a cyclohexane oxidation reactor. The further oxidation of the ketone and alcohol to adipic acid is very complex but occurs in good yield, 94%, despite some succinic and glutaric acid by-products being formed because the adipic acid can be preferentially crystallized and centrifuged. 

Preferential crystallization. Preferential crystallization is one of the oldest methods for the resolution of racemates. It involves seeding of the racemate solution with pure crystals of the desired enantiomer which induce the preferential crystallization of that isomer from the solution. The technology is used in the commercial production of a-methyl-L-dopa (7). 

Another thermal separation unit often used for the laboratory scale purification of ionic liquids is recrystallization [125]. It is an attractive option for those ionic liquids that can form solids with a high degree of crystallinity. Crystals of ionic liquids are expected to be pure because each molecule or ion must fit perfectly into the lattice as it leaves the solution. Impurities preferentially remain in solution as they do not fit as well in the lattice. The level of purity of the crystal product finally depends on the extent to which the impurities are incorporated into the lattice or how much solvent is entrapped within the crystal formed. 

In this section, diastereomeric crystallization is presented as a driving force -or internal selection pressure - to resolve dynamic diastereomeric systems. The dynamic diastereomeric systems are generated from reversible covalent bond formation, leading to compounds carrying chiral carbon centers under thermodynamic control. The dynamic systems can represent more variety of the possible diastereomer adducts. The selective diastereomers, A —B, , are subsequently chosen from the dynamic system by self-transformation and/or self-preferential crystallization. When the selective product C , is formed, the ratio of its corresponding diastereomer adducts A -Bm in the dynamic system will be decreased. The equilibrium in the dynamic system will force the reproduction of the intermediate until the resolution has reached completion. In the end, only one diastereomeric product Cnm is selectively crystallized and easily purified from the solution. 

Resolution by entrainment can sometimes be used to separate racemic mixtures when there are distinct differences in the rates of crystallization of the two optical isomers. This preferential crystallization is initiated by seeding with the crystals of one enantiomer. This technique has been shown to be effective in the production of thiamphenicol (21). 

If left in solution, crystals of a polymorph can convert into other polymorphs (a solvent-mediated transformation). The products of these transformations might be unpredictable and irreproducible. Through kinetic factors in the crystallization, the so-called slurry experiments might mislead in attempts to estimate the relative stability of polymorphs from observations of their interconversion in the presence of solvents. In slurry experiments not the most stable polymorph is formed, but the polymorph growing best under these particular conditions. Preferential crystallization of a polymorph does not directly depend on its relative stability. 

The so-called preferential crystallization is the siii5)lest and the most practical method for optical enrichment of chiral compounds. Applicability of this method for the hydrogenation products witii MNi has been S3 tematically investigated. As summarized in Table 10, all the hydro-genation products are able to be enriched to an optically pure state, without using special and expensive reagents or devices. 

Agitation Speed. Without theoretical explanations agitation is known to enhance the purity drop phenomena or decrease the product purity from the preferential crystallization. We (6) have shown that the product purity drop is decreased by increasing the agitation of the solutions (Figure 9). The increase of the agitation speed from 200 to 400 rpm reduced the purity from about 95 to 80%. Similar tendency was reported by Yokota et al.(7) for SCMC crystallization. 

Experiments were carried out using the D-/L-DOPA (P-(3,4-dihydroxyphenyl) alanine) system with organic acids as the solvents and organic aldehydes as the catalysts for the racemization reaction. Under adequate conditions empirically determined, three rate processes of preferential crystallization, racemization reaction and solvent evaporation proceeded simultaneously at the same rate and the solution composition would then be kept unvaried at the same one as that of initial mixture as shown Figure 14. This process is therefore possible to operate continuously by feeding a conglomerate mixture and by removing the product crystals and the solvents. 

Chiral (L-, or D-form) separation from an optical isomer is essential for its commercial use. Preferential crystallization is often used as a separation technique of a chiral from optic isomers, but it is invalid when racemic compounds are formed, as it is in the production of mandelic acid by chemical reaction. However, by using high pressure crystallization, it becomes possible to separate a chiral from Sie mixture in the region of racemic conq)ound formation under atmospheric pressure, when the eutectic conq)ositions shift toward the racemic composition under high pressure. 

In step X, a racemic product in the ratio 1 1 is isolated. In step X + 1, a chiral auxiliary is added to produce a diastereomeric salt that preferentially crystallizes out of solution and is isolated. In step X + 2, this salt is exposed to acidic or basic aqueous solution to liberate the free optically pure product that is finally collected. In this kind of resolution, half the mass of racemic product collected in step X is destined for waste. Therefore, the percent reaction yield for step X + 1 should be less than or equal to 50%. The reaction yields for steps X and X + 2 can be as high as 100%. The problem is that papers will report the percent yield for step 2 with a fraction that exceeds 50%. How can this be What authors have done is the following sleight of hand. The percent yield they report is not with respect to the starting mass of racemic mixture, but with respect to half its mass, that is, the half that will eventually be collected in step X + 2, assuming no losses along the way. Again, chemists have an... 

The preferential crystallization mechanism is that of volume crystallization. However, surface reactions cannot be neglected when considering crystallization and nucleation in powder compacting and subsequent sintering and crystallization. In these processes, water has a special effect on the production of lithium disilicate glass-ceramics, as demonstrated by Helis and Shelby (1983) and Davis (1997). 

The next stage in the development of a systematic asymmetric synthesis strategy addressed the question of whether or not there was any feedback mechanism whereby the seeding of the initial growth solution with product of one chirality (say D, and formed from an earlier solid state reaction) would modify product formation by induced crystallization such that even more D isomer may be formed on further reaction. Green and Heller proposed a cyclic process as shown in Scheme 6.12a. It transpired, however, that in such experiments the product obtained from a crystal grown in the presence of right-handed product repeatedly caused preferential crystallization into a crystal of the left-handed form — the so-called inversion or reversal rule. ... 

Another form of a direct crystallization is a preferential crystallization, which is also called resolution by entrainment of one enantiomer. The process involves solution formation, e.g., under elevated temperature that will then be subcooled and seeded with crystals of the preferred species. Preferential crystallization is a potent method for the improvement of the product quality and at the same time achievement of a higher yield and productivity. For example, by preferential crystallization of DL-threonine from the aqueous solution, it is possible already during a simple batch to gain highly pure enantiomers up to a certain point after which the opposite enantiomer nucleates from the solution and leads to a purity drop. If (—)-hydrobenzoin seed crystals are added to an ethanol solution of ( )-hydrobenzoin, the ( )-enantiomer will crystallize out and after 15 cycles, 97% optical purity can be obtained. 

F. is one of the most widely distributed monosaccharides (ketohexoses) of the vegetable kingdom and occurs in numerous sweet fiiuts, in vegetables and in flowers. It is also the maj or component ofbees honey. Industrial crystallized products or aqueous solutions are isolated preferentially from mixtures with glucose. 

Catalytic Properties. In zeoHtes, catalysis takes place preferentially within the intracrystaUine voids. Catalytic reactions are affected by aperture size and type of channel system, through which reactants and products must diffuse. Modification techniques include ion exchange, variation of Si/A1 ratio, hydrothermal dealumination or stabilization, which produces Lewis acidity, introduction of acidic groups such as bridging Si(OH)Al, which impart Briimsted acidity, and introducing dispersed metal phases such as noble metals. In addition, the zeoHte framework stmcture determines shape-selective effects. Several types have been demonstrated including reactant selectivity, product selectivity, and restricted transition-state selectivity (28). Nonshape-selective surface activity is observed on very small crystals, and it may be desirable to poison these sites selectively, eg, with bulky heterocycHc compounds unable to penetrate the channel apertures, or by surface sdation. 

Char-liquor advance is simply the removal of mother Hquor from the crystallizer without simultaneous removal of crystals. The primary objective of fines removal is preferential withdrawal from the crystallizer of crystals whose size is below some specified value. Such crystals may be redissolved and the resulting solution returned to the crystallizer. Classified-product removal is carried out to remove preferentially those crystals whose size is larger than some specified value. 

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