Racemic inclusion crystal

A racemic inclusion crystal is also obtained when the guest molecule is other than chloroform. 1 forms a similar 1 1 molecular cavity inclusion complex with methylene chloride, but in a different space group C2/c (Table III). In marked contrast to the type I crystal, the heterocyclophane in the CH Clo complex takes both "R"- and "S"-confor-mations (Type II, racemic inclusion crystal). A schematic picture of the host-guest packing in the methylene chloride complex is shown in Fig 2. 

Urbanczyk-Lipkowska, Zofia, Inclusion Complexation as a Tool in Resolution of Racemates and Separation of Isomers, 8, 1 see also Selective Reactions in Inclusion Crystals, 8, 173. 

In the case of volatile racemic guest, optical resolution can be carried out by using distillation technique in the presence of a non-volatile chiral host compound. The resolution by distillation is summarized in the section of 5. In the section 5, optical resolution by inclusion crystallization in a suspension medium in hexane or water is also described. 

The title compound (131)57 has been found to include a wide variety of solvent molecules as guests and form crystalline inclusion crystals.58 In the inclusion crystallizations, racemates or congromerates of 131 were formed depending on the choice of solvent. In the latter case, the inclusion crystals consisting of one enantiomer of 131 were formed preferentially and the optical resolution of 131 could be performed. 

Tanaka, K., Fujimoto, D., Oeser, T., Imgartinger, H., and Toda, F. (2000) Chiral Inclusion Crystallization of Tetra(p-bromophenyl)ethylene by Exposure to the Vapor of Achiral Guest Molecules A Novel Racemic-to-Chiral Transformation Through Gas-Solid Reaction, Chem. Commun., 413-414. 

Cramer, F., and Dietsche, W. 378 (1959) Occlusion compounds. XV. Resolution of racemates with cyclodextrins, Chem. Ber. 92 b) Toda, F., and Tohi, Y. (1993) Novel optical resolution methods by inclusion crystallization in suspension media and by fractional distillation,/. Chem. Soc., Chem. Commun., 1238-1240 c) Toda, F., and Tanaka, K. (1988) A new chiral host compound... 

Section 2.3.4 deals with a seeding process in the solid state. Racemic 2,2 -dihydroxy-1,T-binaphthyl forms two different kinds of inclusion complex crystals with ether in the host guest ratio, namely, 3 1 and 1 2. Selective inclusion complexation by contact of the racemic host crystal with ether vapor in the solid state can be controlled by adding a seed crystal. 

Table 3.3-10 Formation of racemic 1 1 inclusion crystals of 107 with solvent (guest) molecule.

It is well known that spontaneous resolution of a racemate may occur upon crystallization if a chiral molecule crystallizes as a conglomerate. With regard to sulphoxides, this phenomenon was observed for the first time in the case of methyl p-tolyl sulphoxide269. The optical rotation of a partially resolved sulphoxide (via /J-cyclodextrin inclusion complexes) was found to increase from [a]589 = + 11.5° (e.e. 8.1%) to [a]589 = +100.8 (e.e. 71.5%) after four fractional crystallizations from light petroleum ether. Later on, few optically active ketosulphoxides of low optical purity were converted into the pure enantiomers by fractional crystallization from ethyl ether-hexane270. This resolution by crystallization was also successful for racemic benzyl p-tolyl sulphoxide and t-butyl phenyl sulphoxide271. 

Within this approach, clathrates (for a definition see Chapter 1 in Vol. 140 of this series) and related lattice-type aggregates may be considered as multi-supramolecular systems where guest molecules are included in a crystal matrix. They allow a great many applications which have been specified in Vol. 140, first of all the separation of enantiomers by enantioselective recognition and inclusion of racemic guest molecules. 

An alternative means of obtaining high guest optical purities is simply to add a powdered single crystal of the TOT inclusion compound to a saturated solution of TOT in the racemic solvent. Thus, use of the resolved F6, TOT/2-bromooctane inclusion compound as a seed gave polycrystalline material with an enantiomeric purity of 85% 11S>. 

In this study, D-SCMC seed crystals were put in a racemic SCMC supersaturated solution in a batchwise agitated vessel and growth rates in longitudinal and lateral directions and the optical purity of D-SCMC crystals were measured. The growth rates and optical purity were discussed considering surface states of grown crystal observed by a microscope. The kinetics of crystal growth were measured and a model of inclusion of impurity was proposed. 

Cycloocta-2,4-dien-l-one (95) exists as an equilibrium mixture of the conformers 95a and 95b in solution, and conversion between these two enantiomeric forms is too fast to allow their isolation at room temperature. Photoreaction of 95 in pentane for 1 hr gives racemic 96 in 10% yield along with polymers. When a solution of (—)-ll and 95 was kept at room temperature for 12 h, a 3 2 inclusion complex of (—)-ll with 95a was obtained as colorless needles. Irradiation of the 3 2 complex of (—)-ll with 95a for 48 hr gave (—)-96 of 78% ee in 55% yield. X-ray crystal structure analysis is given in Ref. 51. 

In a typical resolution procedure, two equivalents of a racemic compound and one equivalent of a chiral host dissolved in an inert solvent (toluene, benzene or hexane) are left to crystallize. The resulting crystalline product is an inclusion compound with a typical host guest ratio of 1 1 or 2 1. The guest compound... 

Optically active 19a was previously obtained by inclusion complexation with N -benzylcinchon idi um chloride 21 [36], Compound 21 was also a very efficient resolving agent for rac-17 [37], Crystal structure analysis of a (1 1) complex of 21 and selectively included (+)-17 showed that the molecular aggregate was associated by formation of a Cl HO hydrogen bond. Racemic compound 20 could be efficiently resolved only by complexation with (R,R)-(—)-trans-2,3-bis(hydroxydiphenylmethyl)-l,4-dioxaspiro[4.4]nonane 3b. A crude inclusion complex of 1 1 stoichiometry of 3b was formed selectively with (+)-20 in a 2 1 mixture of dibutyl ether/hexane. One recrystallization from the above combination of solvents gave a 34 % yield of the pure complex. Optically active (+)-20 was obtained by dissolving the complex in 10% NaOH, followed by acidification with HC1 and then recrystallization. The optical purity determined by HPLC (Chiralpack As) was >99.9 %. As far as we know, this is the only report of the resolution of 4,4 -dihydroxybiphenyl derivatives. Conversely, an inclusion... 

Crystallisation of racemic 9 from a variety of solvents results in penannular inclusion compounds where two molecules of the host wrap round one of the guest [30], The resulting molecular pens assemble as layers by means of aryl offset face-face (OFF) interactions (Section 3.1.2). The crystal space groups observed are usually P2i/c, and sometimes C2/c. 

Crystallisation of racemic 15 from either chloroform or 1,1,2,2-tetrachloroe-thane yields achiral inclusion compounds that contain both host enantiomers. In contrast, when 15 is crystallised from tetrahydrofuran (THF), a mixture of (+)- and (—)- crystals is produced in space group /J2 2 2 [40], Once again, chirality arises from the lattice structure rather than from self-resolution of the host enantiomers. 

By crystallization of a mixture of the dipeptide (2) and racemic methyl lactate from methanol, asymmetric recognition occurred to give an inclusion compound that contains the (S)-form of methyl lactate in 89 % ee [20], X-ray crystallographic study of the inclusion compound was able to elucidate that the dipeptide molecules... 

A solution of chiral host and racemic guest compounds in an appropriate solvent is kept at room temperature until inclusion complex crystallizes out. In the complexation, it is necessary to use a solvent which does not form inclusion complex with the host compound. The inclusion complex formed is filtered and purified by recrystallization from solvent, if necessary. Host guest molar ratio is... 

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