Racemic compound mixed crystal

Figure 3. A racemic mixed crystal a packing mode of enantiomers in the crystal with Z = 2 and a binary melting-point phase diagram of (a) disordered type, (b) fairly ordered one (a racemic compound type), (c) fairly ordered one (a racemic conglomerate type), or (d) highly ordered one.

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. 

In contrast, compounds that failed to show Preferential Enrichment such as NTMe3 and NTMe2 have a single convex curve (Figure 9), indicating that these compounds exist only as a single crystalline phase of a racemic mixed crystal composed of the two enantiomers over a wide range of ee values.12,18... 

The crystalline nature and physicochemical properties of the crystals belonging to a racemic conglomerate and a racemic compound have been thoroughly investigated.6 8 In contrast, other types of enantiomers mixture crystals except these two are generally categorized as a racemic mixed crystal, namely, a... 

Thus far three types of stable crystal structures, a-, 8- and e-forms, which are classified as a highly or fairly ordered racemic mixed crystal, have been obtained for the racemic samples of the compounds showing Preferential Enrichment. Among them, the 8-form crystal is most commonly found,10"19 while only one case is observed for each of the a- and e-forms (Table l).91618 It has been confirmed that with respect to ST the formation of the stable a-form crystal is not essential to the occurrence of Preferential Enrichment and is caused by further polymorphic transition of the once-formed 8-form polymorph.22 In this section, the crystal structure of the 8-form is described in detail, because this crystal structure provides a crucial information on the mechanism of the polymorphic transition causing Preferential Enrichment. Another important crystal structure of the e-form is mentioned in detail in the section 7.2. for the same reason. 

We have searched a compound that shows Preferential Enrichment and possesses a homochiral lD-chain structure in the metastable polymorphic form, because it is very possible that the homochiral molecular assembly structure in solution would be retained in the crystal first-formed by crystallization from the same solvent. Finally, racemic NPMe3 was found to possess the desired y-form crystal structure that is classified as a highly ordered racemic mixed crystal and is composed of alternating alignment of homochiral R and S 1D-chains in an antiparallel direction with a space group P-1 (Z = 2) with the... 

The congelation of the mixture furnishes neither racemic compound nor mixed crystals.— This is the simplest case. 

Another peculiarity renders this example, studied by Adriani, very interesting when the temperature is lowered the mixed crystals are seen to transform themselves into crystals of a racemic compound we may construct a portion RJR of the curve, analogous to the congelation curve of a racemic compound within a mixed liquid, which corresponds to this transformation the highest point I of his curve corresponds to the temperature 103. ... 

In cases where the active components can form mixed crystals or solid solutions, the freezing-point curve will exhibit one of the forms given in Figs. 43 and 48. The inactive mixed crystal containing 50 per cent, of the dextro and laevo compound, is known as a pseudo-racemic mixed crystal. So far, only curves of the types I. and II. have been obtained. 

In the case of the carvoximes solid solutions are also formed, but the equilibrium curve in this case exhibits a maximum (Fig. 58). At this maximum point the composition of the solid and of the liquid solution is the same. Since the curve must be symmetrical, this maximum point must occur in the case of the solution containing 50 per cent, of each component, which will therefore be inactive. Further, this inactive solid solution will melt and solidify at the same temperature, and behave, therefore, like a chemical compound (p. 121). The melting-point of the active compounds is 72° that of the inactive pseudo-racemic mixed crystal is 91-4°... 

Koshima and his co-workers have studied the reactivity of co-crystals of acridine and 1-phenyIpropionic acid. This work is analogous to that described last year for the reactivity of acridine with diphenylacetic acid. The present study is summarized in Scheme 2. Again irradiation brings about decarboxylation of the propionic acid and the resulting radical bonds to the acridine. The yields of the compounds and their optical activities are shown below the appropriate structures. When acridine and the acid are irradiated in acetonitrile solution racemic (71) is formed along with the dimer (72). A review of the photochemistry in two-component and mixed crystals systems has been published. ... 

The racemic intermediate of chloramphenicol (AD.HCl) is obtained as a hydrochloride salt during the synthesis, and it is dissolved in water (the free base is low-soluble in water). In this case the resolving agent (0,0 -dibenzoyl-(K,R)-tartaric acid N,N-dimethylamide (DBTADA)) is practically insoluble in water but its ammonium salt is well soluble and it can be prepared easily. The two aqueus solutions are mixed so that the molar ratio between the racemic compound and the resolving agent sould become 1/0.5. The diastereoisomeric salt containing the desired enantiomer (R,R)-AD crystallizes while the hydrochloride salt of (S,S)-AD remains in solution. 

These restrictions might be the cause of some difficulties in crystallizing pure enantiomers. In the case of direct asymmetric synthesis (without prior synthesis of the racemic mixture), it might be interesting to synthesize the antipode and then mix the two enantiomers in order to increase the chance of crystallization. The racemic compound, that is, the racemic co-crystal, is likely to appear it can be used later on as template for the crystallization of the desired pure enantiomer. 

Phase transition is a fundamental defining characteristic of this approach to pure substances. Hence substances that exist in one phase only, easily decompose, only occur in solution, etc. can only be included by analogy. Timmermans [1928, 23-53] lists the following potentially difficult cases for the molar approach of substance definition as summarised in this section azeotropic mixtures, dissociative compounds in equilibrium, enantiomers and racemates ( 18), certain types of mixed crystals or other polymorphic compounds, polymers ( 16), many biochemical compounds, and systems that are not in thermodynamic equilibrium. 

Diastereomeric crystallization. In this approach an optically pure auxiliary compound is added to the mixed optical isomers of the product to form the corresponding diastereomers which are then separated via crystallization. For example, S-naproxen is produced by reacting a chiral amine with the racemic mixture of 2-(6 -methoxy-2 -naphthyl)propionic acid to form the corresponding organoammonium salts of the S- and R- isomers followed by crystallization and reacidification (2). 

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