Racemic crystal

Racemic Crystal-to-Conglomerate Crystal Transformation Reactions in 2,2 -Dihydroxy-1,1 -binaphthyl-l /le4N+CI Complex... 

Many compounds are less soluble as racemates than as their pure enantiomers. It thus appears probable that evaporation of an amino acid solution with a low ee should cause selective precipitation of the racemate crystals, which in turn should lead to an increase of the ee. Extremely simple manipulations, carried out in the chemistry department of Columbia University, led to a drastic increase in enantiomeric excess of phenylalanine 500 mg phenylalanine (with a 1 % ee of the L-component) was dissolved in water, and the resulting solution slowly evaporated until about 400 mg had crystallised out. The remaining solution contained a few mg of phenylalanine with 40% ee of the L-component (i.e., a 70 30 ratio of l to d). If 500 mg of such a solution (40% ee in water) is allowed to evaporate and is separated from the racemate, the result is about 100 mg, with 90% ee of the L-enantiomer (Breslow and Levine, 2006). 

These results for spread film and equilibrium spreading suggest that films of racemic N-(a-methylbenzy 1) stearamide may be resolved by seeding the racemic film with crystals of either pure enantiomer. Indeed, when a monolayer of racemic jV- (a-methylbenzyl) stearamide is compressed to 45 A2/molecule (27 dyn cm-1), deposition of a crystal of either R( +)- or S( — )-enantiomer results in a decay of surface pressure from the initial 28 dyn cm-1 film pressure to 3.0 dyn cm-1, the ESP of the enantiomeric systems on a pure 10n sulfuric acid subphase (Table 1). When the experiment is repeated with racemic crystals, the system reaches an equilibrium surface pressure of 11 dyn cm-1, nearly the ESP of the racemic crystal on the clean acidic interface. In either case, equilibrium pressure is reached within a two hour time period. 

The implication of these results is that deposition of, for example, R( +)-crystals on to the racemic films provides a nucleation site for R( + ) -molecules in the film, leaving behind a partially resolved film of predominantly S( — )-molecules. Deposition of S( — (-crystals should, alternatively, leave behind a film composed predominantly of R( + )-molecules. This model is supported by the ESP data obtained on the clean acidic surface, where the free energy of enantiomer crystals appears to be lower compared with liquid-like film states than that of the racemic crystals. 

As on pure water substrates, the enantiomeric crystals of SSME did not spread on the enantiomeric SSME/palmitic acid monolayer-covered surfaces, while the spreading of the racemic crystals on the racemic film-covered water was actually enhanced. The palmitic acid crystals deposited on either racemic or enantiomeric film covered substrates spread to the same surface pressure, independent of stereochemistry. 

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. 

A low entropy system gets closed, and, according to a process which can be quantitatively described, goes to states of increasing entropy (radioactive decay, racemization, crystal growth, diffusion). 

A prerequisite for application of this method is that within the centrosymmetric racemic crystal a specific functional group attached to an R molecule points toward the face fl but not toward fl (Scheme 12). By symmetry, the same functional group attached to an S molecule will emerge at the enantiotopic face f 1, but not at f 1. Crystallization of a centrosymmetric crystal in the presence of a chiral additive R designed so that it will fit in the site of an R molecule on the growing crystal faces fl or f2, but not on the enantiotopic faces fl or f2,... 

The effect of thr and allothr on the racemic crystals of ser is further manifested independently by dissolution experiments. When rhomblike crystals of ser grown in the presence of (/ ,S)-thr are dissolved in the presence of (fl)-thr, well-formed etch pits develop only at the (011) and (Oil) faces. By virtue of symmetry, similar etch pits form only at the (011) and (Oil) faces when (S)-thr is present... 

An example of the second effect is provided by mono-sec-butyl phthalamide (17a) (56). In the crystal the two enantiomers of this molecule are miscible in all proportions. The racemate crystallizes in space group PI (two general positions in the unit cell) with four molecules per unit cell. Thus there are two molecules in the asymmetric unit. The sec-butyl moieties adopt the anti conformation (the two geometries are shown schematically in 17b) and exhibit conformational disorder to different extents at the two symmetry-independent sites. 

Equilibrium spreading pressures, like static surface tension measurements, provide a means to determine surface energies under equilibrium conditions. On lOA H2SO4, racemic crystals (Fig. 10) spread within 5 min to an equilibrium pressure of 8.6 dynes/cm, whereas about 8 hr was required by either (i )-(+)- or (5)-(-)- crystals to spread to a final pressure of 5.5 dynes/cm. 

A racemic film was compressed nearly to its collapse point. It was then seeded by sprinkling crystals of pure enantiomeric amide on the surface. A rapid decrease in surface pressure was observed approaching the equilibrium spreading pressure of the enantiomer. A control experiment in which racemic crystals were sprinkled on the compressed racemic film produced a pressure drop that slowly approached, but did not reach, the ESP of the racemic film. The observed behavior was consistent with what would be expected if the enantiomer seed crystals had removed molecules of the same enantiomer from the racemic film, leaving a monolayer composed mainly of molecules of the opposite configuration. 

Resolution of helicenes has also been performed by the very laborious method of picking single crystals 4,5 29,79,80). After recrystallization of the partially resolved mixture the procedure can be repeated, until no more variation in optical rotation occurs. Because some helicenes crystallize into racemic crystals by lamellar intergrowth of pure P and pure M forms (see Sect. 6) the crystal picking method is not always applicable, however. A [7]-heterohelicene was partially resolved by crystallization from the chiral solvent54) (—>x-pinene. 

The partially resolved cobalt acetylacetonate was found to be optically stable in solution or in the solid state for long periods. However, slow crystallization of this substance always produced racemic crystals (14). Several of the optically active substituted cobalt chelates exhibited the same strange phenomenon. Removal of the solvent from solutions of optically active cobalt acetylacetonate with a slow stream of air yielded a solid which showed little apparent crystalline character under a polarizing microscope but dissolved to form a solution of about the same specific rotation as the starting solution. 

In the case of NNMe3, the two phase curves were found to intersect at two points around 35% ee (Figure 7).18 The X-ray crystallographic analysis of the nearly racemic crystal indicated that the phase curve in the range of 0 15% ee corresponds to a highly ordered racemic mixed crystal which can hardly be distinguished from a racemic compound (see the section 6.2). On the other hand, the overall flat phase curve in the range of more than 40% ee proved to correspond to a less ordered racemic mixed crystal composed of different amounts of the R and S enantiomers in the crystal lattice. 

Fig. 15.31 Space-filling plot for [7]thia-helicene 33 obtained from the X-ray structure of the racemic crystal.

The compound 1,1 -binaphthyl exists in its stable conformation as a chiral molecule. In the crystalline state, it exists in higher melting (159°C) and lower melting (145°C) forms. The latter form is a racemic crystal in space group C2/c. 

Electron diffraction therefore makes it possible to establish that the structural continuity of the film is ensured. For example, it can differentiate the chiral and the racemic crystal polymorph of a given polymer (it can tell if the selection of helical hands observed in the first layer is still operative in layers deposited subsequently, away from the foreign substrate). As such, electron diffraction probes growth processes taking place in the polymer itself, as opposed to growth on a foreign substrate. Recall that deposition of,... 

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