Optical purity, determination

The optical purities were determined solely from the optical rotations of the (/ -cyanohydrins thus obtained. Only for (/ )-a-hydroxybcnzeneacetonitrile, available from benzaldehyde, was an optical purity determined by comparison with the natural product. Variation of the reaction conditions (pH, temperature, concentration) in water/ethanol led to no appreciable improvementsl4. The use of organic solvents that are not miscible with water, but in which the enzyme-catalyzed reaction can still take place, resulted in suppression of the spontaneous addition to a significant extent, whereas the enzyme-catalyzed formation of cyanohydrins was only slightly slower (Figure l)13. 

This is a member of an interesting class of compounds which are chiral, without actually containing a defined chiral centre. They are chiral because their mirror images are non-superimposable. In the case of this molecule, there is no rotation about the bond between the two naphthol rings because of the steric interaction between the two hydroxyl groups, d and T forms can be isolated and are perfectly stable (Optical purity determination by H NMR, D. R Reynolds, J. C. Hollerton and S. A. Richards, in Analytical Applications of Spectroscopy, edited by C. S. Creaser and A. M. C. Davies, 1988, p346). 

Figure 3. Typical rcvcrsc-phasc-type chromatogram of a diastereomer separation of an aminoelhanol, in this case (ft.S)-propranolol, using an (ft.Si-structure homolog as the internal standard and derivatized with (ft.ft)-DATAAN (Table , Entry 25). This example represents an application for the bioanalysis of a betablocking drug (propranolol), but it can also be used for bulk compound analysis for optical purity determinations.

In any case, in order to ensure reliable results of indirect optical purity determinations using CDAs or for synthesizing optically pure compounds via the formation and separation of covalently bound diastereomers followed by specific cleavage reactions (assuming no racemiza-tion during the building and cleavage reactions), it is mandatory to evaluate and validate the optical purity of CDAs by complementary techniques. 

Optical Purity Determination of Diols with Camphanylboronic Acid... 

Quantitative conclusions regarding the reduction of optical rotatory power of these derivatives by the increased distance of the pairwise interactions must, of course, await optical purity determinations. Qualitatively, however, expectations are obviously confirmed 179 ... 

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... 

FIGURE 6.12 Optical purity determination of pseudoephedrine. Conditions are as in Figure 6.11 [605]. Reprinted with permission from Wiley-VCH Verlag. 

Chiral lanthanide shift reagents represent the most important NMR method for optical purity determination. The potential importance of configuration for chiral drugs has... 

The addition of chiral amines to a,/(-unsaturated sulfoximines has been employed for the resolution of racemic sulfoximines 3 utilizing 0.5 equivalents of a chiral amine in chloroform 117. After completion of the reaction, the unreacted starting material is isolated by column chromatography and its optical purity determined by comparison with the reported optical rotation, or by HNMR using a chiral shift reagent. While (—)-(l/f,2.S,)-2-mcthylamino-1-phenyl-l-propanol [(l/ ,2S)-ephedrine] affords material of moderate optical purity, racemic products are isolated from addition reactions with (—)-l-phenyl-2-propanamine [(—)-am-phetamine] or ( + )-( )-l-phenylethylamine. 

Lammerhoffer, M. and Lindner, W., Optical purity determination of (R)- and (S)-econazole nitrate by enantioselective HPLC Method development and application, Poster presented at the 17th International Symposium on Column Liquid Chromatography, Hamburg 9th - 14th May, 1993. 

Papers of analytical interest include the g.c.-m.s. analysis of the six naturally occurring pyrethrins, g.c. resolution " and optical purity determination of synthetic allethronyl chrysanthemates and ( )-allethrolone (a synthesis of which has been published ), and h.p.l.c. analysis of the six naturally occurring... 

Allenmark, S.G. Chromatographic methods for optical purity determination of drugs. Acta Pharm. Nord. 1990, 2, 161-170. 

A NMR study on the formation of diastereoisomeric inclusion complexes between fluorinated amino acid derivatives and a-CD in 10% D2O solution shows that the chemical shifts of the D-amino acid derivatives included by a-CD are upheld from those of their L analogues [77]. The shift difference between the diastereoisomers formed with D and L enantiomers can be used for chiral analysis and optical purity determinations. For example, the interaction of -CD with propanolol hydrochloride produces diastereomeric pairs. The protons of the antipode give NMR signals which differ in chemical shifts in D2O solution at 400 MHz. The intensity of the resonance signals for each diastereoisomer has been used for optical purity determination. By adding racemate to pure (—) isomer, this technique is able to measure optical purity of propanolol hydrochloride in water down to the level of 1%. 

Chiral Reduction of Ethyl Acetoacetate Optical Purity Determination... 

The observed rotation for a sample isolated by a single student may be only a few degrees, which limits the precision of the optical purity determination. Better results can be obtained if four students combine their resolved amine products for the polarimetric analysis. If you have allowed your amine to have excessive exposure to air, the polarimetry solution may be cloudy. This will make it difficult to obtain an accurate determination of the optical rotation. 

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