Enantiomorphs resolution

A minor chemical use for many of the commoner alkaloids is the resolution of racemic compounds (often acids) into their optically active enantiomorphs. 

Finally, one should be cautioned that, occasionally, substances form chiral single crystals of nearly racemic composition. For example, hexahelicene crystals grown from racemic solutions apparently undergo spontaneous resolution, displaying the enantiomorphic space group P2[2,2, however, the e.e. in the crystal is only —2%. This material (and probably others as well) has a lamellar, twinned structure in which alternating layers, 20 p,m thick, of optically pure (/ )-( + )-and (M)-( — )-hexahelicene are perfectly aligned to build up the observed crystal (266). 

As already mentioned, the secondary alcohols that are obtained are optically active. It should be stressed that the reduction of ketones to carbinols by means of fermenting yeast is completely different from the method of resolution of racemic alcohols by treatment with living microorganisms (Pasteur). In the latter case one of the enantiomorphs is removed by oxidation during metabolism in the former it is produced by true asymmetric hydrogenation, without the intermediate formation of the inactive form, (Cf. Mayer and Levene and Walti. )... 

The observed adsorbate lattice structures show enantiomorphism, that is, adsorption of the right-handed P-heptahehcene (P stands for positive) leads to structures which are mirror images of those observed for M-heptahelicene. This effect can be clearly observed in the high-resolution STM images of Fig. 4.19. Furthermore, the enantiomeric lattices form opposite angles with respect to the [lIO] substrate surface direction. The combined molecule-substrate systems thus exhibit extended... 

The enantiomorphic tetrahydro-2-furylmethanols and certain of their derivatives can also be obtained by resolution of the racemic forms, or by cyclization of a 1,2,5-pentanetriol derivative. For relevant references, see Ref. 115. 

Chirality in Crystals. When chiral molecules form crystals the space group symmetry must conform with the chirality of the molecules. In the case of racemic mixtures there are two possibilities. By far the commonest is that the racemic mixture persists in each crystal, where there are then pairs of opposite enantiomorphs related by inversion centers or mirror planes. In rare cases, spontaneous resolution occurs and each crystal contains only R or only S molecules. In that event or, obviously, when a resolved optically active compound crystallizes, the space group must be one that has no rotoinversion axis. According to our earlier discussion (page 34) the chiral molecule cannot itself reside on such an axis. Neither can it reside elsewhere in the unit cell unless its enantiomorph is also present. 

Similar reactions involving intermolecular quaternization and quaternization/elimination of methyl bromide, using an appropriate alkyl bromide intermediate, led to the formation of the piroarsinolinium bromides (88) and (89) respectively, which were characterized as the iodides. In the case of (88), resolution into optical isomers was also achieved via the (-)-methoxyacetates to give the enantiomorphic iodides ([A/] 132° CHC13) <60JCS9>. 

It should be recalled that whereas the enantiomers in the mixture (or racemate) (1) have identical physical properties (except for their action on the plane of polarised light), the diastereoisomers (2) and (3) have physical properties (e.g. solubility, boiling points, chromatographic behaviour, etc.) which are frequently significantly different. Resolution of the mixture (or racemate) can then be achieved provided that one of the diastereoisomers may be obtained in a pure state, and that regeneration from it of the pure enantiomorphous form is not accompanied by any degree of racemisation. 

Pasteur s original chemical method of resolution, which is still widely used at the present time, involves the formation of diastereoisomeric salts from racemic acids or bases by neutralisation with available optically pure bases or acids respectively. The required optically pure reactants are often available from natural sources and include tartaric, malic and mandelic acids, and alkaloids such as brucine, strychnine, morphine and quinine. Ideally, by appropriate choice of the resolving reagent, the diastereoisomeric salts are crystalline and have solubilities sufficiently different to permit the separation and ready purification of the less soluble salt by fractional crystallisation from a suitable solvent. The regeneration of the optically pure enantiomorph, and incidentally the recovery of the resolving reagent, normally presents no problems. 

Chiral recognition at surfaces occurs at different levels and in different ways. Chiral expression becomes especially obvious in the formation of chiral motifs. That is, chirality is transferred from the single molecule into a supramolecular enantiomorphous structure. Moreover, enantioselective interactions between identical or different species are decisive for spontaneous resolution or play an important role in cooperative phenomena. 

R,R)-TA crystallizes in different enantiomorphous superstructures on Cu( 110), but at a coverage of 0.25 molecules per substrate atom, the monotartrate species forms an achiral c(4 x 2) or (4 0,2 1) structure [71]. In contrast to the bitartrate in its sawhorse geometry, only a single molecular site is connected to the substrate and chirality is not transferred into the lattice structure. Under these conditions, chiral resolution cannot be expected (see below) [72],... 

Although devoid of alkyl chains, [7]H on Cu(lll) forms, similar to 9,10-iodo-octadecanol and the anthracene derivative shown in Fig. 28a, a racemic lattice structure. Conglomerate formation was initially concluded from LEED, because the mirror domain pattern observed for the racemate was identical to the superimposed patterns of the pure enantiomers [92]. STM images, however, delivered different lattice structures for the mirror domains of the racemate and the pure enantiomers [93]. High-resolution STM and MMC finally showed that the enantiomorphous domains are racemic [88]. We will return to this system in more detail in Sect. 4. 

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]. 

Because the optically active forms of the (ethylenediamine)bis-(oxalato)cobaltate(III) ion have been, and will continue to be, excellent resolving agents for many cationic cobalt(III) complexes, it is only proper that a detailed resolution procedure be developed to produce both enantiomorphic forms in useful quantities. 

Replacement of the oxygen ring atom in 30 by sulfur affords a thia-analog with two different solid-state conformations (see 31,32 in Figs. 14 and 15). X-ray crystallography of the crystals showed spontaneous resolution had occurred in which the conglomerate of enantiomorphic chiral crystals contained two symmetry independent molecules of identical configuration in the asymmetric unit of each chiral crystal.1 This is similar to the case for the chiral crystals of 27, but now there are two different conformations instead of only one. One of the chiral crystals showed both... 

Hydroxy-N-methylmorphinan was also found to bind to opioid receptors), but its analgesic activity in the MW assay was of doubtful significance. Related morphinan-6-ones were synthesized via 3-methoxyphenylethyl-amide(76,77) (e.g., Scheme 3.10). Resolution at the 2-benzyltetrahydroiso-quinoline stage afforded (-)-2-hydroxy-N-methylmorphinan-6-one (75a) and the corresponding methyl ether (75b). Neither compound exhibited significant MHP activity,(50) with the ether being only about i x morphine. The (+)-enantiomorphs were prepared in a similar manner.<50)... 

The history of enantiomeric separation starts with the work of Pasteur. In 1848 he discovered that the spontaneous resolution of racemic ammonium sodium tartrate yielded two enantiomorphic crystals. Individual solutions of these enantiomorphic crystals led to a levo and dextro rotation of the polarized light. Because the difference of the optical rotation was observed in solution, Pasteur suggested that like the two sets of crystals, the molecules are... 

---