Chromatography optical resolution

Chromate, tetrakis(dioxygen)-stereochemistry, 94 Chromate, tricyanodiperoxy-structure, 78 Chromate, tris(oxalato)-racemization solid state, 466 strychnine salt racemization, 466 Chromatography optical resolution, 26 Chrome azurol S metallochromic indicator, 556 Chromium... 

Although fractional crystallization has always been the most common method for the separation of diastereomers. When it can be used, binary-phase diagrams for the diastereomeric salts have been used to calculate the efficiency of optical resolution. However, its tediousness and the fact that it is limited to solids prompted a search for other methods. Fractional distillation has given only limited separation, but gas chromatography and preparative liquid chromatography have proved more useful and, in many cases, have supplanted fraetional crystallization, especially where the quantities to be resolved are small. 

Okamoto et al [85] performed the optical resolution of primaquine and other racemic drugs by high performance liquid chromatography using cellulose and amylose tris-(phenylcarbamate) derivatives as chiral stationary phases. Primaquine and other compounds were effectively resolved by cellulose and/or amylose derivatives having substituents such as methyl, tertiary butyl, or halogen, on the phenyl groups. 

On the other hand, telluronium imides 13 were isolated for the first time in 2002 by optical resolution of their racemic samples on an optically active column by medium-pressure column chromatography.27 The relationship between the absolute configurations and the chiroptical properties was clarified on the basis of their specific rotations and circular dichroism spectra. The racemization mechanism of the optically active telluronium imides, which involved the formation of corresponding telluroxides by hydrolysis of the telluronium imides, was proposed (Scheme 6). 

Optical resolution methods with carane-3,4-diol are noteworthy for wide generality. Esters of various cyclopropane carboxylic acids with (1,S, 3A>,4A>,6A>)-carane-3,4-diol were prepared and all (lR)-isomers could easily be obtained by a simple silica gel column chromatography. 

Optical resolution at 25°C of amine salts by solid-liquid chromatography on a silica gel column containing covalently bound (ftR)-host of type [284]°... 

Optical resolution of RCH(C00R )NH3C104 by solid—liquid chromatography using RR-I2851 covalently attached to polystyrene"... 

Racemic modifications may be resolved. There are very few examples of this approach having been employed successfully. The racemic cylic ether (RS)-36, which contains two CH2OCH2CO2H arms attached to the 3 and 3 positions on the axially chiral binaphthyl units, has been resolved (48-50, 93, 94) to optical purity in both its enantiomers by liquid-liquid chromatography using a chiral stationary phase of either (R)- or (S)-valine adsorbed on diatomaceous eaitii. Very recently, the optical resolution of crown ethers (/ S)-37 and (/ 5)-38, incorporating the elements of planar chirality in the form of a rron -doubly bridged ethylene unit, has been achieved (95) by HPLC on (+)-poly(triphenyl-methyl methacrylate). 

Y Ishihama, Y Oda, N Asakawa, Y Yoshida, T Sato. Optical resolution by electrokinetic chromatography using ovomucoid as a pseudo-stationary phase. J Chromatogr A 666 193-201, 1994. 

The hydrocarbon 25 has been partially resolved by asymmetric complexation with Newman s reagent [TAPA ( )-a(2,4,5,7-tetranitro-9-fluorenylideneaminooxy)prop-ionic acid] thereby establishing its chiral Z)2-structure 53). Similarity, the naphthaleno-phane 27b could be resolved by chromatography on silicagel coated with (—)-TAPA 49) and recently also by HPLC on optically active poly(triphenylmethyl methacrylate)49a) which also proved to be very useful for the optical resolution of many other axial and planarchiral aromatic compounds 49b>. 

From other approaches to optically active [2.2]metacyclophanes the following are noteworthy as just mentioned for 64 (medium pressure) liquid chromatography on microcrystalline triacetylcellulose (cf. Ref. 82 ) in ethanol or ether (practicable also at lower temperatures) is a very efficient and successful method for the optical resolution of many axial and planar chiral (aromatic) compounds 83). In many cases baseline-separations can be achieved and thereby both enantiomers obtained with known enantiomeric purity and in amounts sufficient for further investigations, especially for studying their chiroptical properties (see also 3.2 and 3.3). The disub-stituted [2.2]metacyclophanes 57 and 59 (which had been previously correlated to many other derivatives) 78- 79) were first resolved by this method83). 

Introduction of nitrogen into the anulene ring (e.g. of 95) leads to a methano-azaanulene 107 121) with Q-symmetry which is therefore chiral (like its mono- or disubstituted derivatives)118). The low basicity of 107 (pKa 3.20) prevented its optical resolution by conventional methods (e.g. through salts with optically active acids). Excellent results were obtained, however, (as also in the case of the two isomeric carbocyclic methylesters 97 and 101 and of several derivatives of azaanulene) by chromatography on microcrystalline triacetyl cellulose in ethanol at 7 bar 1221 (see also Section 2.7.1). In many cases base line separations were accomplished to give both (optically pure) enantiomers. Enantiomeric relations were confirmed in all cases by recording the CD-spectra of both fractions. Some results of these separations are shown in Fig. 4 together with the optical rotations ([a]D in ethanol) of the enantiomers. 

Ketone mcthylenation can be coupled with concomitant optical resolution effected by chromatography by use of the related reagent 5. The adduct with a prochiral ketone has three asymmetric centers.2... 

Cr(CO)3 coordinates from either the top or bottom side of aromatic rings, bearing two different substituents in ortho or meta position, so that the enantiomers 285 and 286 are obtained. Optical resolution of the enantiomers is carried out by recrystallization, or column chromatography. The racemic complex of benzyl alcohol derivative 287 was separated to 288 and 289 by lipase-catalysed acetylation [68]. Enzymes recognize Cr(CO)3 as a bulky group. Chiral Cr(CO)3-arene complexes are used for asymmetric synthesis [68a]. 

Kaida, Y. and Okamoto, Y. (1993) Optical resolution by high-performance liquid chromatography on benzylcarbamates of cellulose and amylose, J. Chromatogr. 641, 267-278. 

Hopf, H., Grahn, W., Barrett, D.G., Gerdes, A., Hilmer, J., Hucher, J., Okamoto, Y., and Kaida, Y. (1990) Optical resolution of [2.2]paracyclophanes by high-performance liquid chromatography on tris(3,5-dimethylphenylcarbamate) of cellulose and amylose, Chem. Ber. 123, 841-845. 

After the preparation of diastereoisomers by introduction of an optically active resolving agent, the next problem in an optical resolution is to separate the diastereoisomers. It should be recalled that the components of a pair of diastereoisomers necessarily have very similar properties. They contain exactly the same ligands and differ only in their arrangement around the metal atom. Several separation techniques have been used, based either on the fact that diastereoisomers differ in solubility, or in retention time during chromatography. 

The optical resolution was achieved in most cases on an analytical scale by chromatography [52] (see the example in Figure 5.14) using chiral stationary phases of the Chiralcel OD or Chiralpak AD-H type. The separation factors vary between close to 1 and 2.36. 

Unlike the racemic pair ( + )A( + )B and ( —)A( —)B, the diastereoisomeric pair (4-)A( + )B and (+ )A( — )B can also be separated by simple processes (which do not involve chiral agents or influences)—for example, crystallization or chromatography. This is the basis for Pasteur s resolution of ( )-tartaric acid and for countless other similar resolutions. (For a recent account of strategies in optical resolutions, see [30].)... 

S. Allenmark, B. Bomgren, and H. Boren, Direct liquid chromatographic separation of enantiomers on immobilized protein stationary phases III. Optical resolution of a series of A-aroyl d, 1-amino acids by high-performance liquid chromatography onbovine serum albumin covalently bound to silica, /. Chromatogr. 264 (1983), 63-68. 

L. H. Klemm and D. Reed, Optical resolution by molecular complexation chromatography, I. Chromatogr. 3 (1959), 364. 

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