Crystallization procedure, seeded

Scheme 3 The solid yielded by mechanical mixing of the reactants can be used to seed crystal growth from solution to obtain crystals for single-crystal X-ray diffraction experiments. This procedure allows one to compare the X-ray powder diffraction pattern measured on the mechanochemical sample with that calculated on the basis of the single-crystal experiment for the solids obtained by crystallization via seeding of a solution of the ground powder of the adduct...

The crystallization procedure employed by Pasteur for his classical resolution of ( )-tartaric acid (Section 5-1C) has been successful only in a very few cases. This procedure depends on the formation of individual crystals of each enantiomer. Thus if the crystallization of sodium ammonium tartrate is carried out below 27°, the usual racemate salt does not form a mixture of crystals of the (+) and (—) salts forms instead. The two different kinds of crystals, which are related as an object to its mirror image, can be separated manually with the aid of a microscope and subsequently may be converted to the tartaric acid enantiomers by strong acid. A variation on this method of resolution is the seeding of a saturated solution of a racemic mixture with crystals of one pure enantiomer in the hope of causing crystallization of just that one enantiomer, thereby leaving the other in solution. Unfortunately, very few practical resolutions have been achieved in this way. 

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. 

GROWING CRYSTALS WITH SEED CRYSTALS Procedure ... 

Figure 5.1 shows the procedure for preferential crystallization. Mutual seedings of small amounts of crystals of both enantiomers of a racemate to a supersaturated solution of the racemate alternatively give large amounts of the corresponding enantiomers. Thus, the preferential crystalhzation is very simple and therefore a fascinating way to obtain both enantiomers of a racemate. However, preferential crystalhzation is not always apphed to any racemate. 

Crystallization Method. Such methods as mechanical separation, preferential crystallization, and substitution crystallization procedures are included in this category. The preferential crystaUization method is the most popular. The general procedure is to inoculate a saturated solution of the racemic mixture with a seed of the desired enantiomer. Resolutions by this method have been reported for histidine (43), glutamic acid (44), DOPA (45), threonine (46), A/-acetyl phenjialanine (47), and others. In the case of glutamic acid, the method had been used for industrial manufacture (48). 

The first method is the classical technique of Pasteur, which entails the mechanical separation of enantiomorphic crystals formed simultaneously while the mother liquor remains racemic. Enantiomer separation by this particular method is extremely time-consuming and is really impossible unless the crystals form with well-defined hemihedral faces. Nevertheless, it is often the method of choice to obtain the seed crystals required for other direct crystallization procedures. When a particular system has been shown to be a conglomerate, and the crys-... 

There are also a limited number of mechanical separation procedures basically similar to that originally used by Pasteur to separate the different tartaric acids. Such methods usually require the use of special crystallization techniques, or the use of chiral additives such as cyclodextrin. These types of crystallization procedures, however, can be somewhat tedious to operate and not usually applicable. Nevertheless, a limited number of processes have been successfully established, where a concentrated racemic solution is carefully maintained at a critical temperature and then seeded with one isomer only. Under these conditions the crystals produced are almost entirely of that of a single isomer only. However, these are rather special cases and the field of application for mechanical separation methods, in general is rather limited. 

Crystallization. The crystallization procedure is taken from that described by Fujii et For crystallization experiments, the Sulfolobus sp. ferredoxin solution obtained from a preparative Sephadex G-50 gel filtration column (Amersham Pharmacia Biotech) is concentrated by pressure filtration through an Amicon YM3 or YMIO membrane at 4° and made to 5 mg/ml in 0.5 M Tris-maleate-NaOH buffer, pH 5.0, containing 1% 2-methyl-2,4-pentanediol. Crystals suitable for X-ray diffraction analysis are obtained by a batch method performed under aerobic conditions. Fine-powdered ammonium sulfate is slowly added to 300 p.1 of 5 mg/ml protein solution until the turbidity is observed to persist (1.9-2.1 M). The crystallization solution is stored at 37° in an incubator. Dark brown crystals with appropriate dimensions of 0.3 x 0.3 x 0.5 mm are obtained in 3-5 weeks. Fujii etaO reported that reproducibility of the crystallization is enhanced by seeding a drop of the mother liquor containing microcrystals into the crystallization solution just before the crystallization begins. 

Although a number of methods for optical resolution of D,L-tryptophan have been reported, most of them employed chemical or enzymatic procedures and only a few reports on preferential crystallization procedures have appeared [see ref. (756) for a review]. Recently Yamada et al. (448) made use of the benzenesulfonate of D,L-tryptophan for optical resolution by preferential crystallization. Seeding a supersaturated solution of the sulfonate salt with the crystals of L-tryptophan brought about preferential crystallization of the L-isomer, while the D-isomer remained in the mother liquor. 

The simplest and cheapest procedure to obtain standards is based on selective extraction followed by crystallization. A method developed to obtain lycopene from tomato residue using factorial experimental design consisted of a preliminary water removal with ethanol, followed by extraction with EtOAc and two successive crys-talhzation processes using dichloromethane and ethanol (1 4), producing lycopene crystals with 98% purity, measured by HPLC-PDA. Using this approach, bixin was extracted with EtOAc from annatto seeds that were previously washed with... 

Erudc acid is a constituent of various natural oils but is most conveniently obtained from rape seed oil. The process described above is essentially that of Reimer and Will.1 Methods have been developed for obtaining pure erudc add free from saturated acids,2 but these involve time-consuming procedures of fractional precipitation and crystallization, and necessarily give poor yields. The product obtained above is satisfactory for most purposes. 

Mullin(3) has used this procedure for the design of a unit for the crystallisation of potassium sulphate at 293 K. The data are given in Table 15.5 from which it will be noted that the cross-sectional area depends linearly on the relative degree of de-supersaturation and the production rate depends linearly on the area but is independent of the height. If the production rate is fixed, then the crystalliser height may be adjusted by altering the sizes of the seed or product crystals. Mullin and Nyvlt(75) have proposed a similar procedure for mixed particle-size in a crystalliser fitted with a classifier at the product outlet which controls the minimum size of product crystals. 

Figure 10.2 Schematic of the experimental procedures involved for two common zeolite synthesis methods including in situ crystallization and secondary (seeded) grow.

Mechanical Separation of Crystals. The first instance of resolution was by L. Pasteur who was able to resolve crystals of sodium ammonium tartrate (which recrystallizes in two distinct, nonsuperimposable forms below 2TC). Although this procedure is rarely used, one might be able to seed a racemic solution resulting in only one... 

In this section, a brief description of the necessary experiments to identify the kinetic parameters of a seeded naphthalene-toluene batch crystallization system is presented. Details about the experimental apparatus and procedure are given by Witkowski (12). Operating conditions are selected so that the supersaturation level is kept within the metastable region to prevent homogeneous nucleation. To enhance the probability of secondary nucleation, sieved naphthalene seed particles are introduced into the system at time zero. 

To determine the rate of dissolution of hemlhydrate crystals, the same vessel was used as for the crystallization study. The vessel was filled with the sulphate-rich solution (zero Initial calcium concentration). An amount of sieved hemlhydrate seed crystals, about 10% In excess of that required to saturate the solution, was added. At very short time Intervals, samples were taken using a similar procedure to that for the gypsum growth Investigation. Samples were separated Into crystals for size analysis (with a 190pm orifice) and crystal content and solutions for analysis. Further details are given by Mukhopadhyay (17). 

The experimental procedure was as follows. One litre of supersaturated aqueous solution was prepared, of which 0.8 was poured Into the crystallizer. After a constant temperature (of 298.2 K) was attained, the solution concentration was determined, and a seed crystal (0.59-0.71 mm) was put Into the solution and was allowed to grow for either 600 or 900 s. The crystal was then taken out of the crystallizer and put Into a 50 ml beaker In which a small quantity of alcohol was placed. The crystal was removed from the beaker and dried In the air for a few mlnltes, then Its weight and surface area were measured. The same crystal was again placed Into the crystallizer and allowed to resume growth. 

---