Enantiomorphic crystal

In 1822, the British astronomer Sir John Herschel observed that there was a correlation between hemihedralism and optical rotation. He found that all quartz crystals having the odd faces inclined in one direction rotated the plane of polarized light in one direction, while the enantiomorphous crystals rotate the polarized light in the opposite direction. 

The manual separation of the enantiomorphous crystals of sodium ammonium tartrate tetrahydrate (Figure 1) by Pasteur in 1848 (1) is historically significant, because it laid the foundations of modem stereochemistry. This experiment demonstrated for the first time that certain classes of molecules display enan-tiomorphism even when dissolved in solvent. These observations eventually paved the way for the inspired suggestion, made more than two decades later, by van t Hoff (2) and Le Bel (3), of a tetrahedral arrangement of bonds around the carbon atom. 

Figure I. Enantiomorphous crystals of sodium ammonium tartrate -4H20.

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. 

The etching of an enantiomorphous pair of asn crystals in the presence of (/ )-aspartic acid and () )-A-methylasparagine is illustrated in Figure 12. Under these conditions, only the R crystals are etched (Figure 12a), whereas the S crystals dissolve smoothly (Figure 12b). The dramatic differences in the surfaces of the two enantiomorphous crystals after dissolution again make it possible to perform a manual Pasteur-type sorting of the R and S crystals with a quantitative enantiomeric yield. 

We illustrated in Section II why conventional X-ray diffraction cannot distinguish between enantiomorphous crystal structures. It has not been generally appreciated that, in contrast to the situation for chiral crystals, the orientations of the constituent molecules in centrosymmetric crystals may be unambiguously assigned with respect to the crystal axes. Thus, in principle, absolute configuration can be assigned to chiral molecules in centrosymmetric crystals. The problem, however, is how to use this information which is lost once the crystal is dissolved. 

As illustrated for compounds 77 and 78 in Scheme 18, different methods were applied for the syntheses of 77-79 (79 was obtained analogously to 78 according to method a). The racemic products 77a 0.7CH3CN, 78 CH3CN, and 79 were isolated as crystalline solids. In addition, crystals of the racemic compound 77b (an isomer of 77a) were obtained. For the solvent-free compound 78 formation of enantiomorphic crystals was observed. The crystals studied by X-ray diffraction contained (just by accident) the (A)-enantiomer. 

Crystallization and reactivity in two-dimensional (2D) and 3D crystals provide a simple route for mirror-symmetry breaking. Of particular importance are the processes of the self assembly of non-chiral molecules or a racemate that undergo fast racemization prior to crystallization, into a single crystal or small number of enantiomorphous crystals of the same handedness. Such spontaneous asymmetric transformation processes are particularly efficient in systems where the nucleation of the crystals is a slow event in comparison to the sequential step of crystal growth (Havinga, 1954 Penzien and Schmidt, 1969 Kirstein et al, 2000 Ribo et al 2001 Lauceri et al, 2002 De Feyter et al, 2001). The chiral crystals of quartz, which are composed from non-chiral Si02 molecules is an exemplary system that displays such phenomenon. 

A few examples of the Cl (l), that is, the 1C (d) conformation have been described. /3-D-Arabinopyranose and its enantiomorph crystallize in this conformation (Ia2e3e4a),1(i as illustrated in formula 20 for the /3-D compound. The Cl (d) conformer is shown, for comparison, in formula 21. As may be seen, neither form has any large nonbonded interactions. Both forms have one axial hydroxyl group on... 

A question which may sometimes be asked is this If an enantio-morphous crystal- -that is, one possessing neither planes, nor inversion axes, nor a centre of symmetry—is dissolved in a solvent, does the solution necessarily rotate the plane of polarization of light The answer to this question is, Not necessarily . If the molecules or ions of which the crystal is composed are themselves enantiomorphous, then the solution will be optically active. But it must be remembered that enantiomorphous crystals may be built from non-centrosymmetric molecules which in isolation possess planes of symmetry—these planes of symmetry being ignored in the crystal structure such molecules in solution would not rotate the plane of polarization of light. (A molecule of this type, in isolation, may rotate the plane of polarization of light (see p. 91), but the mass of randomly oriented molecules in a solution would show no net rotation.) An example is sodium chlorate NaC103 the crystals are enantiomorphous and optically active, but the solution of the salt is inactive because the pyramidal chlorate ions (see Fig. 131) possess planes of symmetry. 

Topochemical Polymerization The chiral crystalline environment of a monomer itself can be a source of asymmetric induction in solid-state polymerization [69-72], Prochiral monomers such as 37 give enantiomorphic crystals, one of which can be preferentially formed by recrystallization with a trace amount of optically active compounds. Photoir-... 

Fig. 5 Solid-state CD spectroscopic analysis of two enantiomorphous crystals of hippuric acid...

Figure 35, Top Enantiomorphous crystals of sodium ammonium tartrate. Hemihedral facets are marked by an h. Bottom (+)-(2R,3R)-tartaric acid (left) and (-)-(2S,35)-tartaric acid (right).

Chiral surfaces Enantiomorphous crystals Homochiral peptides Mirror symmetry breaking Non-linear kinetics Self-replication of peptides... 

Crystallization processes comprise two sequential steps crystal nucleation followed by crystal growth. Kondepudi et al. demonstrated in a series of experiments that spontaneous symmetry breaking may be induced by growing crystals of non-chiral molecules such as sodium chlorate, binaphthyl, and p, p -dimethyl-chalcone, which crystallize as enantiomorphous crystals of... 

A similar effect has been reported in the crystallization of non-chiral molecules, where the presence of small amounts of chiral additive forces the entire system to crystallize in an enantiomorphous crystal, which upon further solid-state reaction can be converted into polymers of a single handedness [184,185]. Chiral auxiliaries, which affect crystal nucleation enantios-electively, have been successfully used for the large-scale optical resolution of enantiomers [186-188]. 

Racemic and enantiomorphous 2-D and 3-D crystals display different physical and chemical properties. This difference has been utilized to enhance chirality in non-racemic systems that self-assemble in racemic and enantiomorphous crystallites. Morowetz [196] has elaborated a mathematical model that considers an evaporation/crystallization process where the racemate is less soluble than the pure enantiomorphous crystal and the enantiomer (in excess) is concentrated in the solution. A similar enrichment of chirality has... 

When two enantiomorphous right- and left-crystals are separately obtained, one can conveniently use each crystal for the seeding of the selective chiral crystallization to either one of the two enantiomorphous crystals. More elegant pseudoseeding, based on utilizing different crystals with similar crystal structure as seed crystals, can enantiocontrol crystallization from solutions of tryptamine and achiral carboxylic acids [35]. 

Achiral 3,4-bis(diphenylmethylene)-A-methylsuccinimide 102 crystallized in three polymorphic forms, one of which was chiral in space group P2X. Irradiation of the enantiomorphous crystal (+ )-102 gave the optically active photocyclization product ( + )-103 in 64% ee (Scheme 24) [95]. This enantioselective photoconversion consists of two steps, a conrotatory ring closure and a 1,5-hydrogen shift. The latter sigmatropic reaction occurs in the solid state in a suprafacial manner. 

Pure Si02 occurs in only two forms, quartz and cristobalite. The silicon atom is always tetrahedrally bound to four oxygen atoms, but the bonds have considerable ionic character. In cristobalite the Si atoms are placed as are the C atoms in diamond with the O atoms midway between each pair. In quartz there are helices, so that enantiomorphic crystals occur, and these may be easily recognized and separated mechanically. 

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