Racemic solid solution

Certain pairs of enantiomers, such as 25°C solutions of camphor in aqueous ethanol (Fig. 26a), 2,2,5,5-tetramethyl-l-pyrrolidinoxy-3-carboxylic acid in chloroform (Fig. 26b), or carvoxime in hexane (Fig. 26c), cocrystallize throughout the entire range of mole fractions. The crystals that are in equilibrium with the saturated liquid solution are solid solutions (mixed crystals), since they constitute a single phase. The racemic solid solution is termed a pseudoracemate [141]. 

Racemic solid solution. The phase-composition diagram has a zero slope across the whole composition range thus, there is little difference in the affinity among molecules of either configuration (i.e., no chiral discrimination). 

If one enantiomer has similar affinity for molecules of eidier configuration, dten die enantiomers are randomly distributed in die crystal and die solid is a racemic solid solution or mixed crystal. Such solids are identical with eidier enantiomer (Figure 6.4). 

Crystalline states of racemates are generally classified into the following three forms racemic mixture (conglomerate), racemic compound, and racemic solid solution (Figure 1). 

Characteristic Conglomerate True racemate Psuedoracemate or racemic solid solution... 

There is a third form of solid state organization of racemic compounds, called the sohd solution or pseudoracemic compound. This is a rare form in which the arrangement of the enantiomers in the crystal is variable and not defined. The significance of this is that, while the stoechiometry of the two enantiomers in the whole crystal may well be 1 1, it is possible to find homochiral unit cell structures, one enantiomer being substituted for the other. Such disorder arises from the strong similarity of the two enantiomers, particularly in the case of quasispherical molecules. This arrangement is also called a racemic solid solution of the two enantiomers. 

In such cases, the racemic modification shows nearly ideal mixing and forms a racemic solid solution (pseudoracemate or mixed crystal) [13,14]. 

Pseudo-racemates are solid solutions (mixed crystals) of equimolecular proportion of the (+) and (—) enantiomer. Quasi-racemates are racemic solid solutions involving two very similar chiral substances. 

Pseudoracemate, which is a racemic solid solution containing equal numbers of molecules of opposite enantiomers in a more or less random arrangement. By the addition of a small amount of one enantiomer, the melting point will be not changed or such changes are negligible. 

Plouvier then prepared the previously unknown racemic form of proto-quercitol by mixing equal weights of the two enantiomers. The melting point (237°C.) of the mixture was not depressed, and its (presumably solid state) infrared spectrum reportedly (36) was identical with that of either active form. It thus appears that DL-proto-quercitol exists as a solid solution, not a racemic compound or conglomerate. 

Kellogg RM, Kaptein B, Vries TR (2007) Dutch Resolution of Racemates and the Roles of Solid Solution Formation and Nucleation Inhibition. 269 159-197 Kessler H, see Weide T (2007) 272 1-50... 

Fig. 23 Tie lines associated with different systems (1) a solid phase D (pure enantiomer) in the presence of mother liquor of variable composition, (2) a solid phase L, (solvated enantiomer) in mother liquor of variable composition, (3) a solid phase R (pure racemic compound) in mother liquor of variable composition, (4) a solid phase Rs (solvated racemic compound) in mother liquor of variable composition, (5) two solid phases, one enantiomer and the racemic compound (or two enantiomers if E is on SR, i.e., for a conglomerate) in mother liquor of fixed composition E (eutectic), and (6) the tie lines do not converge one solid phase is present (solid solution of D and L) in mother liquor of variable composition. (Reproduced with permission of the copyright owner, John Wiley and Sons, Inc., New York, from Ref. 141, p. 177.)...

Racemate - Traditionally, a 1 1 mixture of enantiomers was denoted racemic mixture. In order to describe precisely the solid state according to distinct phases racemates (or racemic compounds), conglomerates and solid solutions were distinguished. Thus, the term race-mate had a very specific function. However, currently the term racemate is almost exclusively used in the general sense of racemic mixture. It appears sensible to comply to current usage and reserve the term racemic compound to a distinct solid phase. 

From the list of space groups in Table 24 it follows that hexahelicene crystals are apparently chiral. This is also true for crystals of hexahelicene grown from racemic solutions. However, dissolved single crystals of [6] display optical rotations which show only about 2 % enantiomeric excess instead of 100 %. Solid solutions are unlikely in this case (m.p. racemate 231-233°, optically pure [6] 265-267 °C) and ordinary twinning can also be rejected. 

The method relies on the p and n salts having different solubilities, and they must not form solid solutions or double salts. The more insoluble salt is filtered and the purified acid recovered by adding mineral acid. This method of chiral resolution is well established, and lists of resolving agents for many classes of racemic compounds are available [22], Inclusion chemistry may be employed for the same purpose by preparing host-guest compounds with a chiral host ... 

The formation of two-dimensional nanocrystals, by peptide amphiphiles is also influenced by the chirality of the peptide building block.125 Three types of two-dimensional crystals were observed after the assembly of the functionalized peptide amphiphiles 17-19 shown in Figure 7.11 (above) at the air-water interface, which was followed by polymerization. These two dimensional crystals include (/) a racemic compound, in which each enantiomer is packed with its mirror image in a crystalline order, (it) enantiomorphous conglomerates, in which each enantiomer is segregated into small domains, and (iii) a solid solution, in which all molecules are randomly distributed without crystalline order. Interestingly, in the case of the two-dimensional system arising from the racemic compound,... 

Both modifications of the method depend upon a natural segregation of the molecules of each active component into their individual crystal lattices. Experience has shown that such segregation, though common for dissimilar solutes, seldom occurs in the solution of a racemic substance and then usually in a narrow range of conditions that cannot be predicted or attained readily. In the great majority of instances the molecules of both active components combine in equal numbers to form one species of crystals known as a racemic compound or combine in variable proportions to form a series of solid solutions. Also, when segregation does occur, the experimental procedure necessary to produce distinguishable crystals or a uniform deposit of one variety is usually troublesome and slow. Hence the method has assumed practical value only in a few instances in which all the circumstances are especially favorable. 

Crystals interact with molecules of the environment via the surfaces that delineate them. Consequently, several of their properties, such as their morphology, structure and symmetry of solid-solutions and their etch-pit patterns formed upon partial dissolution, depend on an interplay between the surface structures of the crystal faces and the composition of the solution. For example, crystallization of a racemate undergoing spontaneous resolution in the... 

Optically active [Fe(phen)3]2+ and [Fe(bipy)3]2+ are readily obtained (via the antimony d-tartrate439). Racemization in the solid-state is very slow and available kinetic results have been discussed in a recent review.440 The volume of activation for racemization of crystalline [Fe(phen)3](C104)2 has been estimated441,442 to be —0.9 + 0.1 cm3 mol 1 at room temperature. The volume of activation for racemization in solution is positive and large (14,2 + 0.3 cm3 mol-1 in... 

For convenience, a phase diagram of a pair of diastereomeric crystals is ordinarily studied in detail, and the mechanism of the diastereomeric resolution is interpreted in terms of the thermodynamic and physical properties of the bulk of the diastereomeric crystals.4,7-10 Such studies reveal the importance for diastereomeric resolution of the type of mixture of diastereomers in a target system. There are three types of diastereomer mixtures an eutectic mixture, a 1 1 addition compound, and a solid solution. To achieve successful resolution, it is essential that the mixture of the diastereomeric crystals of a target racemate with a resolving agent be an eutectic mixture. The classic studies are thoroughly reviewed by Collet and co-workers.4,12... 

Of the three types of racemates,11 conglomerate, racemic compound, and solid solution, 3-(1,2-dihydroxyethyl)-1,5-dihydro-3H-2,4-benzodioxepine shows melting point behavior characteristic of a racemic compound. The racemic diol is much higher melting than the enantiomerically enriched diol as shown in the Figure 1. Therefore the diol of lower ee precipitates first during recrystallization and the enantiomerically enriched diol remains in the mother liquor. High ee diol (97% ee) is then obtained upon recrystallization of this mother liquor. 

A brief description of the type of "racemic" compounds is necessary for the reader to better understand the principles behind the application of crystallization methods to the separation of enantiomers. Three fundamental types of crystalline racemates exist. In the first, the crystalline racemate is a conglomerate, which exists as a mechanical mixture of crystals of two pure enantiomers. The second, which is the most common, consists of the two enantiomers in equal proportions in a well-defined arrangement within the crystal lattice this is termed racemic compound. The third possibility occurs with the formation of a solid solution between the two enantiomers that coexist in an unordered manner in the crystal. This kind of racemate is called a pseu-... 

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