Spontaneous crystallization

This is the method which allowed Pasteur to discover molecular chirality 150 years ago [2]. The prerequisite for working of this technique is the occurrence of a chiral compound as a crystalline conglomerate (racemic mixture) rather than a racemic compound. In bulk, such a conglomerate is optically inactive. However, individual crystals contain only one enantiomer. This is not the case for a racemic compound which does not form a conglomerate. In the latter case crystals contain equal amounts of both enantiomers. 

The theory and experiment of direct crystallization of enantiomers is quite well understood at present [10]. There are a number of variables which affect the resolution by direct crystallization in practice. Several technological schemes based on this principle are realized on the commercial scale. These are, for example, the Merck process used for the production of antihypertensive drug methyldopa [11], a process developed by Harman and Reimer for (-)-menthol, which is separated as an ester [12], the process patented by Industria Chimica Profarmaco for the resolution of naproxen enantiomers as the ethylamine salt [13], the production of L-glutamic acid by the Japanese company Ajinomoto on a scale in excess of 10000 tons annually as early as the 1960s [14], etc. In general, it seems that spontaneous crystallization is a very useful technique for the enantioseparation of the naturally occurring a-amino acids. All of them may be resolved either directly or as derivatives [10]. 

The important advantage of a direct crystallization is that a chiral compound does not necessarily possess functional groups which are required for diastereomeric salt formation. The disadvantages include its limited applicability because less than 10% of all crystalline race-mates occur as a conglomerates, poor predictability and very sensitive dependence from the experimental conditions. Thus, as mentioned by some authors, even Louis Pasteur would not have succeeded with his very first enantioseparation had he performed the experiment with the mixed cesium-rubidium salt of tartaric acid at temperatures higher than 27 °C [4]. 

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The chemist can try to separate the two isomers by careful fractional distillation but it will be next to impossible to do because both the cis and the trans have practically the same boiling point. There are a few things that the chemist can do or hope for to get rid of that cis isomer. The cis configuration is less stable than the trans and may switch over to the trans configuration with a little help. The chemist can gently heat the isosafrole oil to about 150°C for an hour or so. She can also try the same heating except have the oil mixed with some acetic acid. Also, the isosafrole can be fractionally distilled to ultra purity and then be allowed to simply sit for a couple of days. Trans isosafrole may spontaneously crystalize out while the cis form remains as an oil. They can then be separated by filtration. 

Stretching a polymer sample tends to orient chain segments and thereby facilitate crystallization. The incorporation of different polymer chains into small patches of crystallinity is equivalent to additional crosslinking and changes the modulus accordingly. Likewise, the presence of finely subdivided solid particles, such as carbon black in rubber, reinforces the polymer in a way that imitates the effect of crystallites. Spontaneous crystal formation and reinforcement... 

In terms of spontaneous crystallization, the assumption that N nuclei commence to grow simultaneously at t = 0 is the most unrealistic. We can modify the model to allow for sporadic, spontaneous nucleation by the following... 

Miers, H.A. and Isaac, F., 1907. The spontaneous crystallization of binary mixtures. Proceedings of the Royal Society, A79, 322-351. 

The aqueous layer Is separated and washed with ether, the ether extracted with 5% hydrochloric acid, the acidic solution is made basic with 10% sodium hydroxide and again extracted with ether. Since some spontaneous crystallization occurs in the ether, the solvent is removed without drying under vacuum and the residue is recrystallized from 35 ml of ethanol giving 18.0 g of 1-cyclopropylmethyl-5-phenyl-7-chloro-1 H-1,4-benzodiazepine-2(3H)-one, MP 145° to 146°C (65% yield), according to U.S. Patent 3,192,199. 

Benzoyl-6-deoxy-6-iodo-2,3-0-isopropylidene-a-i, - xylohexulofura-nose (47). A solution of 15 grams (31.3 mmole) of 46 in butanone (200 ml.) containing dry sodium iodide (9.3 grams, 62 mmole) was refluxed for 24 hours. The reaction mixture was cooled, the sodium tosylate removed by filtration, and the filtrate concentrated to dryness. The residue was partitioned between water (50 ml.) and chloroform (2 X 50 ml.) the combined chloroform solutions were washed with water, dried over sodium sulfate and concentrated to a colorless sirup which spontaneously crystallized. Recrystallization from aqueous methanol afforded pure material in two crops (11.6 grams, 85%), m.p. 115°-117°C, [ ]D24 + 36.0° (c, 5.3). Anal Calcd. for C16H1906 C, 44.2 H, 4.4 I, 29.3. Found C, 44.3 H, 4.5 I, 29.4. 

Method B (one-pot procedure)-. 5 g (33 mmol) of L-arabinose. 12 mL of ethanol and 4mL (36.7 mmol) of bcnzylaminc arc heated on a steam bath for 5 to 10 min to give a clear solution. After cooling, 2.5 mL of anliyd hydrogen cyanide are added. Spontaneous crystallization of the product begins within a few minutes. After cooling for 2 h with an ice-bath, the product is isolated by filtration and washed with ethanol yield 7.0-7.5g (79-85%) nip 129-131 C after recrystallization from ethanol mp 130-132 C. 

Studies of large, randomly assembled cellular automata... have now demonstrated that such systems can spontaneously crystallize enormously ordered dynamical behavior. This crystallization hints that hitherto unexpected principles of order may be found [and] that the order may have significant explanatory import in [biology] and... physics. 

As the temperature is decreased, the chains become increasingly rigid zc then approaches 1 if we assume that there is only one fully ordered crystalline structure and Zconf for the liquid becomes smaller than 1. This means that, at this level of approximation, the disordered state becomes less favorable than the crystalline ground state. A first-order disorder-order phase transition is expected to occur under these conditions. Flory interpreted this phase transition as the spontaneous crystallization of bulk semiflexible polymers [12], However, since the intermolecular anisotropic repulsion essential in the Onsager model is not considered in the calculation, only the short-range intramolecular interaction is responsible for this phase transition. 

The copolymers consist of strictly alternating sequences of diene and olefin. C-NMR measurements Showed the microstructure of the butadiene units in BPR to be exclusively of the trans-1,4 configuration (Figure 8). The isoprene units in isoprene-ethylene copolymer (IER) contain 84 % trans-1,4, 15 % cis-1,4, and 1 % 3,4 structures (Figure 9). Spontaneous crystallization in unstretched BPR samples was detected by dilatometry and confirmed by X-ray diffraction and DSC measurements. The extrapolated equilibrium melting point is about -10 °C. 

Vigorous boiling of solvent occurs during addition of the carbodiimide and during spontaneous crystallization of the product. Approximately 250 ml. of ether was used. 

The dextrose monohydrate obtained today by the foregoing method is a high grade product practically pure chemically. Where higher purity is occasionally desired, this product is recrystallized by essentially the same methods as described earlier.18 The absence of appreciable amounts of impurities renders crystallization somewhat easier. Nevertheless, the tendency for uncontrolled spontaneous crystallization is still encountered so that care is necessary in cooling the mass at the... 

Spontaneous resolution seems to be a general phenomenon, because it is also observed to occur from solutions of achiral sodium chlorate, which crystallizes into morphologically chiral crystals. In the same way as quartz, however, any given spontaneous crystallization produces nearly equal numbers of left- and right-handed sodium chlorate crystals. The explanation for this behavior is that the primary crystallization nuclei that form throughout a cooling concentrated solution must occur with a random distribution of the two morphological chiralities. 

TABLE 6.2. Entropy Change in Spontaneous Crystallization of Water"... 

Absolute asymmetric synthesis refers to the situation in which an asymmetric induction occurs in the absence of an externally imposed source of chirality [5]. Such reactions are invariably carried out in the crystalline state, where the asymmetric influence governing the enantioselectivity derives from the spontaneous crystallization of an achiral compound in a chiral space group. This phenomenon, which is analogous to the spontaneous crystallization of racemates as... 

The distilled dlamide Is a pale yellow oil at room temperature It freezes in the refrigerator (+4 C) If seeded within some hours. The first spontaneous crystallization took several weeks. It can also be obtained as snow white crystals from diisopropyl ether/hexane, rap 15-16°C. 

The seed crystal Is obtained by dissolving a sample ( 1 g) of the crude imidazolium salt in a minimum amount of acetonitrile (3 mL) this solution is allowed to stand at -30°C overnight. The checkers observed spontaneous crystallization upon removal of volatile materials. 

It was found for spontaneous crystal growth of ribosomal particles that the lower the Mg concentration, the thicker the crystals Consequently, crystals from 508 subunits from H. marismortui, grown spontaneously under the lowest Mg concentration possible, were transferred as seed crystals to solutions with even a lower Mg concentration. As a result, after about two weeks well ordered and relatively thick crystals of about 0.6 x 0.6 x 0.2 mm were formed (Fig. 7) that diffracted to about 6 A... 

The simplest method relies on equilibration of the enantiomers in solution from which one of the enantiomers is obtained by spontaneous crystallization ( Spontaneous Resolution ). Al-... 

A number of glass-crystalline materials (GCM) have been proposed for immobilization of HLW. They can be classified in two groups those produced by spontaneous crystallization, and those formed by induced (catalytic) crystallization. 

Spontaneous crystallization usually occurs within 30 minutes. If it does not, crystallization is induced by scratching the bottom of the reaction flask. 

SYNTHESIS A solution of 0.67 g 5-hydroxyindole (indol-5-ol) in 10 ml dry MeOH was treated with a solution of 0.30 g NaOMe in MeOH, followed by 0.70 g benzyl chloride. The mixture was heated on the steam bath for 0.5 h, and the solvent removed under vacuum. The residue was suspended between H20 and CH2CI2, the organic phase separated and the aqueous phase extracted once with CH2CI2. The combined organics were stripped of solvent under vacuum, and the residue distilled. A colorless fraction came over at 170-190 °C and spontaneously crystallized in the receiver. There was obtained 0.90 g (80%) 5-benzyloxyindole with a mp 81-86 °C which increased, on recrystallization from toluene / hexane, to 94-96 °C. A sample prepared from the decarboxylation of 5-benzyloxyindole-2-carboxylic acid has been reported to have a mp of 102 °C from benzene. 

As discussed in section 2.2.5, the solubility of lactose is temperature dependent and solutions are capable of being highly supersaturated before spontaneous crystallization occurs and even then, crystallization may be slow. In general, supersolubility at any temperature equals the saturation (solubility) value at a temperature 30°C higher. The insolubility of lactose, coupled with its capacity to form supersaturated solutions, is of considerable practical importance in the manufacture of concentrated milk products. 

In the absence of nuclei and agitation, solutions of lactose are capable of being highly supersaturated before spontaneous crystallization occurs. Even in such solutions, crystallization occurs with difficulty. Solubility curves for lactose are shown in Figure 2.6 and are divided into unsaturated, metastable and labile zones. Cooling a saturated solution or continued concentration beyond the saturation point, leads to supersaturation and produces a metastable area where crystallization does not occur readily. At higher levels of supersaturation, a labile area is observed where crystallization occurs readily. The pertinent points regarding supersaturation and crystallization are ... 

Spontaneous crystallization can occur in the labile area without the addition of seeding material. 

If ice-cream is warmed or the temperature fluctuates, some ice will melt, and an infinite variety of lactose concentrations will emerge, some of which will be in the labile zone where spontaneous crystallization occurs while others will be in the metastable zone where crystallization can occur if suitable nuclei, e.g. lactose crystals, are present. At the low temperature, crystallization pressure is low and extensive crystallization usually does not occur. However, the nuclei formed act as seed for further crystallization... 

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