Crystallization and racemization

The initial product is recrystalLized and filtered. The filtrate contains a 65% yield (99% ee) of the R-isomer. The crystals ate racemic (32% yield 8%... 

There is one exception to this statement. In a very few cases, racemic mixtures may cry stalize from solution in such a way that all the (+) molecules go into one crystal and the (—) molecules into another. If one of the crystals crystallizes before the other, a rapid... 

Thermolysis of 1-phenyl-3,4-dimethylphosphole in alcoholic solvents in the presence of NiCl2 leads to the synthesis of the racemic biphospholene complex (222).653,654 Upon reaction of the bromo derivative with AgBF4, the meso and racemic diastereomers of (223) are formed, which can be separated by fractional crystallization.655 In both (222) and (223) the coordination sphere is slightly distorted from square planar. 

Conventional methods for separating organic compounds, such as crystallization and distillation, fail to separate racemic mixtures. 

Enantiomeric recognition was clearly displayed in films spread from solution and films in equilibrium with their crystals, and was sharply dependent on the acidity of the subphase. Protonation of the amide group appeared to be necessary for spreading to stable monolayers. For example, the crystals of the racemate deposited on a 10n H2S04 solution at 25°C spread quickly to yield a film with an ESP of 7.7 dyn cm"1, while the single enantiomers spread only to a surface pressure of 3.9 dyn cm-1 (Table 1). Similar effects are observed at 15 and 35°C. The effect of stereochemistry on equilibrium spreading is even more pronounced at lower subphase acidities. On 6n sulfuric acid, the racemate spread to an equilibrium surface pressure of 4.9 dyn cm-1, while the enantiomeric systems spread to less than 1 dyn cm-1. 

The Yl/A isotherms of the racemic and enantiomeric forms of DPPC are identical within experimental error under every condition of temperature, humidity, and rate of compression that we have tested. For example, the temperature dependence of the compression/expansion curves for DPPC monolayers spread on pure water are identical for both the racemic mixture and the d- and L-isomers (Fig. 13). Furthermore, the equilibrium spreading pressures of this surfactant are independent of stereochemistry in the same broad temperature range, indicating that both enantiomeric and racemic films of DPPC are at the same energetic state when in equilibrium with their bulk crystals. 

Fig. 27 Equilibrium spreading pressure versus film composition for crystals of palmitic acid and racemic and enantiomeric stearoylserine methyl ester deposited on palmitic acid/SSME monolayers (a) enantiomeric crystals on enantiomeric SSME/palmitic acid films (b) racemic crystals on racemic SSME/palmitic acid films (c) palmitic acid crystals on either racemic or enantiomeric SSME/palmitic acid films.

Conversely, the racemic film system appears to be solubilized by the achiral fatty acid component. At compositions of 10-33% palmitic acid, the ESP of the racemic system varies linearly with film composition, indicating that the monolayer in equilibrium with the racemic crystal is a homogeneous mixture of racemic SSME and palmitic acid. At compositions of less than 33% palmitic acid, the ESP is constant, indicating that three phases consisting of palmitic acid monolayer domains, racemic SSME monolayer domains, and racemic SSME crystals exist in equilibrium at the surface. 

For a number of the systems, comparisons were made between the effects of enantiomeric composition in the monolayer and corresponding melting-point-composition curves for the crystals. All of the latter gave clear evidence of racemic compound formation in the crystals, and this type of pattern was repeated in the monolayer properties. 

The famous crystallographer/chemist Misterlich had previously published that crystals of tartaric acid and racemic acid salts were isomorphous (identical in shape). Indeed, in spite of the differing influence of tartaric acid and racemic acid on plane-polarized light, many of the great scientists of the day were convinced that tartaric acid and racemic acid were the same compound. As it turned out, these scientists were both right and wrong. 

Crystals composed of the R and S enantiomers of the same racemic mixture must be related by mirror symmetry in terms of both their internal structure and external shape. Enantiomorphous crystals may be sorted visually only if the crystals develop recognizable hemihedral faces. [Opposite (hid) and (hkl) crystal faces are hemihedral if their surface structures are not related to each other by symmetry other than translation, in which case the crystal structure is polar along a vector joining the two faces. Under such circumstances the hemihedral (hkl) and (hkl) faces may not be morphologically equivalent.] It is well known that Pasteur s discovery of enantiomorphism through die asymmetric shape of die crystals of racemic sodium ammonium tartrate was due in part to a confluence of favorable circumstances. In the cold climate of Paris, Pasteur obtained crystals in the form of conglomerates. These crystals were large and exhibited easily seen hemihedral faces. In contrast, at temperatures above 27°C sodium ammonium tartrate forms a racemic compound. 

A solution or melt of a racemic mixture of enantiomers may crystallize either as a racemic phase or as a mixture of two resolved enantiomorphic phases. The molecules in these two enantiomorphic phases will be exact mirror images of one another. However, a given enantiomer, say R, will have different environments in the racemate and in the resolved crystal and will be conformationally different. Correspondingly, the R molecule in the resolved crystal and the S molecule in the racemate will not be exact mirror images. 

All the crystal forces that we treat in this section can be considered in terms of the recognition between a given, reference molecule and the cavity it is to occupy in the crystal. In chiral systems the cavity is clearly of different shape in the d and / crystals, and this generally results in differential incorporation of R and S molecules. However, in molecules containing the sec-butyl group, discrimination is often ineffective. This is because the two enantiomers can assume different conformations with very similar external shapes, and they can then interchangeably enter the same cavity in the crystal. This effect was recognized some time ago (55), and recently its consequences have been studied in detail (56). In the case where two enantiomers may readily replace one another in the crystal, it follows that there is a tendency to conformational disorder (see biphenyl, above), and in many cases, the resolved enantiomers and the racemates are isostructural. 

In 1969 Calvin [64] proposed a scheme for autocatalytic symmetry breaking, which he called stereospecific autocatalysis . Calvin s mechanism has been validated experimentally in the context of the total spontaneous resolution during the crystallization of racemic mixtures. During crystallization, crystals of one enantiomer may spontaneously separate, leaving the other enantiomer in solution. If the possibility of the equilibration of the enantiomers in solution exists and if the enantiomer in solution can convert rapidly to the enantiomer that is crystallizing before crystallization is complete, then the entire racemate may deposit as a single enantiomer. At least half a dozen examples of Calvin s stereospecific autocatalysis involving such... 

Optically active EP is an important C3 chiral building block for the synthesis of chiral pharmaceuticals such as j9-adrenergic blockers [11 -13], vitamins [14,15], pheromones [16], natural products [17], and new materials such as ferro-electric crystals [18]. Racemic EP can be made via 2,3-DCP and l,3-dichloro-2-pro-panol (1,3-DCP) synthesized from propylene by organic synthesis [19] however, a practical production method for optically active EP has not yet been established. Racemic 2,3-DCP, which is easily synthesized by the chemical... 

Photolysis of cycloheptenecarbothioamide 24d in the solid state also gave the corresponding p-thiolactam in specific yield (entry 7). As the X-ray crystallographic analysis revealed, the crystal is racemic (Fig. 9), and the isolated p-thiolactam was obtained as racemate. 

Similarly the term isotactic was applied by Price and Osgan (78) to the crystalline polymer obtained from optically active and racemic propylene oxide. The zigzag and Fischer representations of an isotactic poly(propylene oxide) are shown in 36 and 37 (Scheme 7). Their different appearance is due, as already explained in a similar case, to the odd number of chain bonds existing in each monomer unit. Formula 36 presents alternately substituents on both sides of the chain and is very similar to the actual structure observed in the crystal state (79). 

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