Resolution, enantiomers

Crystallization Method. Such methods as mechanical separation, preferential crystallisation, and substitution crystallisation procedures are included in this category. The preferential crystallisation method is the most popular. The general procedure is to inoculate a saturated solution of the racemic mixture with a seed of the desired enantiomer. Resolutions by this method have been reported for histidine (43), glutamic acid (44), DOPA (45), threonine (46), A/-acetyl phenylalanine (47), and others. In the case of glutamic acid, the method had been used for industrial manufacture (48). 

Table 10 Result of one-pot preparation method of optically active epoxides (67a-d) by a combination of epoxidation of cyclohexenone and enantiomer resolution in a water suspension medium... 

The use of dissociable diastereomers for enantiomer resolution may be illustrated by the case where racemic mandelic acid is resolved using en-antiomerically pure a-methylbenzylamine. The n and p salts of a-methylbenzyl-amine mandelate have aqueous solubilities of 49.1 and 180 g/L, respectively, at 25°C [153], A more recent example, which focuses on the crystallographic origin of the solubility differences, is provided by the resolution of ( )-mandelic acid with (-)-ephedrine in water or methanol solution [154], In general, the relative solubilities of the n and p salt pairs are strongly influenced by the choice of solvent medium and temperature, which provide considerable flexiblity in optimizing the crystallization conditions and the efficiency of resolution. This process may be facilitated by the development of a full solubility phase diagram. 

Figure 1-13. Chiral metal chelates for enantiomer resolution by complexation gas chromatography.

As discussed in part 2.2.3 biocatalysis may be used both in asymmetric synthesis and resolution in order to obtain enantiopure compounds. A major difference between asymmetric synthesis and resolution is that the former in theory may give 100% yield of the wanted enantiomer. Resolution on the other hand can only give 50% yield since the starting point is a mixture of 50% of each enantiomer. This is the classical disadvantage of resolution. 

In general, sulfoximines are accessible by various routes, and most of them involve sulfur oxidation/imination sequences. For example, enantiopure 9 is commonly prepared starting from sulfide 10, which is oxidized with hydrogen peroxide (under acidic conditions) giving sulfoxide 11 (Scheme 2.1.1.1). Subsequent imina-tion of 11 with a mixture of sodium azide and sulfuric acid affords sulfoximine 9 as a racemate. Enantiomer resolution can then be achieved with camphorsul-fonic acid, leading to both enantiomers of 9 with high efficiency [15]. Alternatively, many sulfoximine syntheses start from enantiopure sulfoxides [16, 17], which can be stereospecifically iminated with 0-mesitylenesulfonylhydroxyl-amine (MSH) [18], as shown for the synthesis of sulfoximine (1 )-13 in Scheme 2.I.I.2. 

Werkhoff P, Bretschneider W, Giintert M, Hopp R, Surburg H (1991) Chirospecific analysis in flavor and essential oil chemistry. Part B. Direct enantiomer resolution of trans-a-ionone and trans-a-damascone by inclusion gas chromatography. Z Lebensm Unters Forsch 192 111 Larsen M, Poll L (1990) Odour thresholds of some important aroma compounds in raspberries. Z Lebensm Unters Forsch 191 129... 

The integration of a catalyzed kinetic enantiomer resolution and concurrent racemization is known as a dynamic kinetic resolution (DKR). This asymmetric transformation can provide a theoretical 100% yield without any requirement for enantiomer separation. Enzymes have been used most commonly as the resolving catalysts and precious metals as the racemizing catalysts. Most examples involve racemic secondary alcohols, but an increasing number of chiral amine enzyme DKRs are being reported. Reetz, in 1996, first reported the DKR of rac-2-methylbenzylamine using Candida antarctica lipase B and vinyl acetate with palladium on carbon as the racemization catalyst [20]. The reaction was carried out at 50°C over 8 days to give the (S)-amide in 99% ee and 64% yield. Rather surpris-... 

The fundamentals of structure and stereochemistry have been considered in previous chapters in some detail. There are, however, practical aspects of stereochemistry that have not yet been mentioned, particularly with regard to chiral compounds. How, for instance, can a racemic mixture be separated into its component enantiomers (resolution) what methods can be used to establish the configuration of enantiomers how can we tell if they are pure and how do we synthesize one of a pair of enantiomers preferentially (asymmetric synthesis) In this chapter, some answers to these questions will be described briefly. 

FIGURE 16 Effects of acetonitrile percentage on the enantiomic resolution of (a) RS-2-(4-bromo-2-fluorobenzyl)-(l,2,3,4-tetrahydropyrrolo[l,2-a]pyrazine-4-spiro-3 -pyrrolidine)-l,2, 3,5 -tetrone on Chiralpak AD-RH and (b) Chiralcel OD-RH, and (c) flubiprofen on Chiralpak AD-RH CSP at different temperatures. (From Refs. 91, 92.)... 

Table 11. Enantiomer resolution by fractional distillation in the present of a chiral host...

Toda, F., and Ochi, M. (1996) Enantioselective Oxidation of Imines in Inclusion Complexes with a Chiral Host Compound and Preparation of Optically Pure Oxaziridines by Enantiomer Resolution, Enantiomer, 1, 85-88. 

Toda, F., Tanaka, K., Watanabe, M., Abe, T., and Harada, N. (1995) Enantiomer Resolution by Crystallization with Chiral Host Application to Monoterpenes, Verbenone and Apoverbenone, Tetrahedron Asymm., 6, 1495-1498. 

Schurig, V. and Biirkle, W. (1982) Extending the scope of enantiomer resolution by complexation gas chromatography, J. Amer. Chem. Soc. 104, 7573-7580. 

Separation of a racemic compound has been called optical resolution or simply resolution . Nowadays, the descriptions enantiomer resolution or enantiomer separation are also commonly used. Accordingly, Enantiomer Separation is used in the title of this book. The editor and all chapter contributors hope that this book is helpful for scientists and engineers working in this field. 

Bulk Capsules Mianserin TLC TLC Dissolve in methanol Shake contents with methanol, filter Silica Chloroform-methanol- ZM ammonium hydroxide (85 14 I) Ninhydrin BP, addendum 1983. p. 243 TLC [1] GC [2] HPLC [3] enantiomer resolution [703] [4]... 

Prazepam Bulk TLC Silica ammonium hydroxide (99 1) S, - EtOAc-MeOH- HPLC [3] Enantiomer resolution by HPLC [703, 707] hRn = 81, hRp = 85. [132]... 

R. W. Souter, Gas chromatographic resolution of enantiomeric amphetamine and related amines. II. Effect of cyclic structures on diastereomer and enantiomer resolution, J. Chromatogr., 114 301 (1975). 

P. Rashidi-Ranjbar, Y.-M. Man, J. Sand-strom, H. N. C. Wong, Enantiomer Resolution, Absolute Configuration and Attended Thermal Racemization of Two Tetrabenzocydooctatetraene (o-Tetra-phenylene) Derivatives. An Exceptionally High Barrier to Ring Inversion, J. Org. Chem. 1989, 54, 4888-4892. 

Y. Dobashi, K. Nakamura, T. Saeki, M. Matsuo, S. Hara, and A. Dobashi, New chiral polysiloxane derived from (R,R)-tartramide for enantiomer resolution by capillary gas chromatography,/. Org. Chem. 56 (1991), 3299. 

Finally, mention may be made of those articles in which this method is utilized in the synthesis of optically active oxiranes for example, the simple synthesis of monosubstituted (S)-oxiranes and the asymmetric cyclization of some chlorohydrins catalyzed by optically active cobalt (salen)-type complexes, or in the enantiomeric selection of racemic oxiranes via halohydrins and /3-hydroxy sulfides. A useful three-step synthesis has been worked out from (S)-amino acids to (R)-alkyloxiranes as well as enantiomer resolution for chiral oxiranes by complexation gas chromatography. ... 

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