Enantiomeric purity estimation

The regioselectivity of this reaction is excellent (92 8), and the diastereomeric purity of 2 is estimated to be 93% de on the basis of the oxidation of 2 to (5)-2-cyclohexen-1-ol (93% ee). Similarly, the reaction of 2 with acetaldehyde provides (S.iS H- -cyclohexeny ethanol with an enantiomeric purity of 92% cc. Reactions of 2 with other aldehydes, however, have not yet been reported. 

The optical purity was determined by chiral GC, using a 20 % permethylated cyclodextrin column, after esterification of the pure product with (CF3C0)20 in dry CH2CI2 (65 °C isothermal carrier gas N2, pressure 70 kPa). T r = 26.305 min (>99%, (3R,45)-3-allyl-4-hydroxy-2-pentanone). The enantiomeric purity was estimated to be >99 % and the diastereomeric purity >99 %. 

Marini, R. D., Servais, A.-C., Rozet, E., Chiap, P., Boulanger, B., Rudaz, S., Crommen, J., Hubert, P., and Fillet, M. (2006). Nonaqueous capillary electrophoresis method for the enantiomeric purity determination of 5-timolol using heptakis(2,3-di-0-methyl-6-0-sulfo)-p-cyclodextrin validation using the accuracy profile strategy and estimation of uncertainty. /. Chromatogr. A 1120(1—2), 102-111. 

When 1 is added to a solution of a mixture of enantiomers, A and A, it associates differently with each of the two components to produce the diastereo-meric complexes A+ 1 and A 1. The nmr spectrum of the mixture then shows shift differences that are large compared to the uncomplexed enantiomers (because of the paramagnetic effect of the europium) and normally the resonances of the A+ 1 complex will be distinct from those of the A 1 complex. An example of the behavior to be expected is shown in the proton nmr spectrum (Figure 19-4) of the enantiomers of 1-phenylethanamine in the presence of 1. Although not all of the resonances are separated equally, the resolution is good for the resonances of nuclei closest to the metal atom and permits an estimate of the ratio of enantiomers as about 2 1 and the enantiomeric purity as 33%. 

The L-(-)-proline was established by the checkers to be of >99.8% (estimated level of detection) enantiomeric purity by conversion to N-pentafluoropropionyl-L-(-)-proline isopropyl ester and GLC analysis on a 50-m glass capillary column containing the chiral phase, Chirasil-Val (Quadrex Inc.). Analyses were performed on a Hewlett-Packard HP 5710 A instrument operated isothermally at 140°C. Racemic proline was used as a control. 

In a normal NMR experiment in, say, CDC13 or CC14, it is not possible to distinguish enantiomers or estimate enantiomeric purities. However, by the use of three separate techniques that all involve some diastereomeric component, it is possible to determine enantiomeric purities of, for example, alcohols, esters, ketones and amines. 

To assess the stereospecificity of the Grignard and organolithium reactions with menthyl phosphinates, the diastereomeric purity of starting menthyl esters was estimated by pmr spectroscopy (see Sect. 2.2) and, in most cases, highest reported rotations were used to estimate the. enantiomeric purity of the derived optically active phosphine oxides The method of preference for determining the enantiomeric purity of a phosphine oxide, even in those cases in which a value for the rotation of optically pure material is reported, involves stereospecific reduction of the phosphine oxide with hexa-chlorodisilane (see Sect. 2.4) to the corresponding phosphine, followed by quatemization with 2-phenyl-2-methoxy-ethyl bromide and pmr analysis of the diastereomeric phosphonium bromides (Eq. (1)) > This method for determining optical purity, shown ) to be applicable... 

Figure 3.8 Estimation of the enantiomeric purities of the enantiomers of JH III by using a chiral solvating reagent in1H NMR measurements (400 MHz, CDCb). Modified by permission of Shokabo Publishing Co., Ltd...

Accordingly, estimation of A+ and A of a sample by an appropriate physical method such as GC, HPLC and NMR enables the calculation of its enantiomeric purity.12... 

When a crystalline enantiomer is obtained, although the observation of unchanged melting point and specific rotation upon further crystallization, is, in principle, not a reliable criterion of its being enantiomerically pure, nonetheless, this criterion has often led to correct estimates of enantiomeric purity of optically active organosilicon compounds. 

To ensure high enantiomeric purity of the product there should be <0.5% 1,1 -bi-2-naphthol or its monoester in this solution. The relative amounts of binaphthol species can be accurately determined by HPLC on a reverse-phase column eluted with a water-acetonitrile gradient (50-100% over 10 min). Both 1,1 -bi-2-naphthol and its dipentanoate have equal (within 2%) extinction coefficients at 254 nm. The monopentanoate absorbs more strongly the relative extinction coefficient at 254 nm is 1.13. Alternatively, the solution composition can be estimated using thin layer chromatography silica gel eluted with 1 4 ethyl acetate/cyclohexane 1,T-bi-2-naphthol, Rf 0.39 monopentanoate, Rf 0.56 dipentanoate, Rf 0.71. 

Currently, the most widely practised procedure for the quantitative estimation of diastereoisomeric purity (d.e.) and thus of enantiomeric purity (e.e.) consists in the derivatization of the aminoalkyl phosphonic acid as the A-(3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl) derivative the latter is prepared from (R)-(+)-(3,3,3-trifluoro-2-methoxy-2-phenyl)propanoyl chloride (the so-called Mosher reagent) Although the diastereoisomeric derivatives 123 may also be separable by HPLC (e.g. on Zorbax-Sil) and which can be separately characterized [the derivative from (+)-Val was shown by X-ray... 

Many chiral saturated hydrocarbons are known in nonracemic form. Some are natural products or derivatives thereof others are products of synthesis. Absolute configurations have been established by chemical correlations with substances of known configuration by changes not affecting the stereogenic atomsIn many cases the enantiomeric composition can be estimated by comparisons with samples that have been fully resolved or by extended correlations with substances that have been analyzed by modern methods for the assessment of enantiomeric purity. This permits calculation of maximum rotations and these are, where possible, reported here. Observed rotations, ol, have been corrected for tube length (/ = 1 dcm) when necessary and are reported as such when corrections for density or concentration (p in gml" ) have not been made by authors. Specific rotations ... 

Calculated for sample estimated to have enantiomeric purity of 68%- Calculated for sample estimated to have enantiomeric purity of 96%-... 

An interesting method for the estimation of optical purity of sulfoxides, which consists of the combination of chemical methods with NMR spectroscopy, was elaborated by Mislow and Raban (241). The optical purity is usually determined by the conversion of a mixture of enantiomers into a mixture of diastereomers, the ratio of which may be easily determined by NMR spectroscopy. In contrast to this, Mislow and Raban used as starting material for the synthesis of enantiomeric sulfoxides a diastereomeric mixture of pinacolyl p-toluenesulfinates 210. The ratio of the starting sulfinates 210 was 60.5 39.5, as evidenced by the H NMR spectrum. Since the Grignard reaction occurs with full stereospecificity, the ratio of enantiomers of the sulfoxide formed is expected to be almost identical to that of 210. This corresponds to a calculated optical purity of the sulfoxide of 20%. In this way the specific rotations of other alkyl or aryl p-tolyl sulfoxides can conveniently be determined. 

MIP assays can also be utilized in synthetic organic applications. For example, MIP-based assays have been used to measure the chiral purity of samples in organic solvents. An L-phenylalanine anilide (l-PAA) imprinted polymer was utilized as a recognition element to measure the enantiomeric excess (ee) of PAA samples (Chen and Shimizu 2002). The MIP displays greater capacity for l-PAA versus d-PAA samples of similar concentration, and this difference was used to estimate enantiomeric excess. The enantiomeric excess of an unknown solution was determined by comparing the UV absorbance of the PAA remaining in solution after equilibration against a calibration curve. This MIP assay was demonstrated to be rapid and accurate with a standard error of +5% ee. 

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