Conglomerates, crystallization

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

Conglomerate crystallization in the above case indicates that the inclusion approach may be further extended into the realm of the salt-type associates. Such an attempt is especially interesting due to the obvious role in enantiomer separation which relies heavily on the solubility difference of the enantiomeric salts under certain circumstances 137). 

G. B. Kauffman, I. Bernal and H.-W. Schiitt, Overlooked opportunities in stereochemistry, Part IV. Eilhard Mitscherlich s near discovery of conglomerate crystallization on the sesquicentennial of Pasteur s resolution of sodium ammonium racemate , Enantiomer, 1999, 4, 33—45. 

Spontaneous asymmetric synthesis has been envisaged by theoretical models for more than 50 years [1-7]. This process features the generation and amplification of optical activity during the course of a chemical reaction. It stands in contrast to asymmetric procedures, such as stoichiometric resolution, conglomerate crystallization, or chiral chromatography, in which the optical activity can be increased but no additional chiral product is formed [8]. It is also different from classical asymmetric synthesis, in which new chiral product is obtained but the resulting enantiomeric excess (ee) is usually less than or, at most, equal to that of the chiral initiator or catalyst1. 

The formation of the comparatively more stable heterochiral dimers generates an optically inactive reservoir that consequently leads to an increase in the ee of the free monomers. In this case, the ee is increased by building up an inactive racemic pool, as is the case in conglomerate crystallizations. 

Both of the racemic crystals of the piperidine and pyrrolidine complexes have chiral space groups before irradiation. The most important requirement for the racemic-to-chiral transformation is that the two molecules with R and S configurations crystallize in a chiral space group. Since the racemic compounds tend to make a pair around an inversion center in the process of crystallization, the racemic crystals, in general, have a center of symmetry. Otherwise, conglomerate crystals may be deposited from a racemic solution. Therefore, only several crystals with chiral space groups have been reported so far [38]. This may be a reason that such a racemic-to-chiral transformation has not been observed till now. 

D.K. Kondepudi, K.E. Crook, Theory of conglomerate crystallization in the presence of chiral impurities, Cryst. Growth Des. 5 (2005) 2173-2179. 

K. Saigo, H. Kimoto, H. Nohira, K. Yanagi, M. Hasegawa, Molecular recognition in the formation of conglomerate crystal the role of cinnamic acid in the conglomerate crystals of 1-phenylethylamine and l-(4-isopropylphenyl)ethylainine salts. Bull. Chem. Soc. Jap. 

The history of the crystallization of stereoisomers is fascinating. Pasteur noted the visible difference in morphology between crystals of the isomers of ammonium sodium tartrate in 1848. This turned out to be a fortuitous circumstance as ammonium sodium tartrate happens to crystallize as conglomerate crystals, that is, a eutectic mixture containing crystals of the two pure isomers. Such behavior has since been found to be infrequent, although it has proved industrially important. Pasteur separated the crystals manually to achieve the first documented isomeric separation ... 

The achiral salt, N-(2-hydroxyethyl)-N,N,N-trimethylammonium chloride (111) was found to form a mixture of two 1 1 inclusion complexes lOb-111 and lOc-111 as conglomerate crystals, but not the racemic complex lOa-111. The result strongly suggests that enantiomeric separahon of 10a can easily be done by complexahon with 111. lOb-111 and lOc-111 crystals can easily be separated mechanically. By re-peahng the seeding experiments as shown in Scheme 3.3-3,10b of 99% ee and 10c of 99.5% ee were finally obtained in 66 and 64% yields, respechvely [49]. 

We have seen in Section 2.2 that racemic compounds can exist in three crystalline forms racemic compounds, conglomerates and pseudo-racemic compounds, each of which has particular properties. Thus, racemic compounds and conglomerates crystallize in forms whose space groups are centro- and noncentrosymmetric respectively. The crystallization of enantiomers always leads to noncentrosymmetric structures. 

Other methods for racemate separation include fractional crystallization of diaster-eomers with optically pure counter ions [304], conglomerate crystallization [305], and various chromatographic techniques incorporating both mobile and stationary chiral phases [306]. All of these techniques involve intermolecular interactions of some kind. While it is theoretically possible to model these, by using molecular mechanics, the complexity of the problems involved have so far been prohibitive when the time required for a thorough design is compared with experimental trial-and-error studies. 

Fig. 2. The composition of enantiomeric mixtures obtained by crystallization (ee) in fimction of starting enantiomeric purity (eeo). a), conglomerate melting point diagram b). racemate melting point diagram The diagrams of expected results of c). conglomerate crystallization, d). racemate crystallization, e) kinetic-conglomerate like crystallization...

Ejgenberg M, Mastai Y. Conglomerate crystallization on self-assembled monolayers. Chem. Commun. 2011 47 12161-12163. 

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