Determining Optical Purity

There are several ways to determine the optical purity of a compound obtained as the product of an enantioselective synthesis. The simplest technique involves measuring the optical rotation using a polarimeter (Sec. 7.5). The reported specific rotation, of pure methyl (S)-(-)-3-hydroxybutanoate is +38.5° 

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Fig. 2. Chromatogram showing (a) the Ic separation of A, (+) (T)-(l-ferrocenyl-ethyl)thioethanol B, (+) 1-ferrocenyl-l-methoxyethane and C, (+) 1-mthenocenylethanol, on a 25-cm P-cyclodextrin column (see Table 2), and (b) the potential use of a P-cyclodextrin column to determine optical purity...

Because process mixtures are complex, specialized detectors may substitute for separation efficiency. One specialized detector is the array amperometric detector, which allows selective detection of electrochemically active compounds.23 Electrochemical array detectors are discussed in greater detail in Chapter 5. Many pharmaceutical compounds are chiral, so a detector capable of determining optical purity would be extremely useful in monitoring synthetic reactions. A double-beam circular dichroism detector using a laser as the source was used for the selective detection of chiral cobalt compounds.24 The double-beam, single-source construction reduces the limitations of flicker noise. Chemiluminescence of an ozonized mixture was used as the principle for a sulfur-selective detector used to analyze pesticides, proteins, and blood thiols from rat plasma.25 Chemiluminescence using bis (2,4, 6-trichlorophenyl) oxalate was used for the selective detection of catalytically reduced nitrated polycyclic aromatic hydrocarbons from diesel exhaust.26... 

NIRA provides a non-destructive alternative to differential scanning calorimetry for the determination of polymorphic forms of drugs, e.g. the polymorphic forms of caffeine. NIRA has also been used to determine optical purity. While the pure opposite enantiomers of a substance have identical NIR spectra, mixing two... 

A method for determining optical purities of less than one percent for secondary alcohols has been published, and Mislow has observed a partial resolution which may serve to distinguish between a meso and a racemic host product when a derived inclusion compound is recrystallized from an enantiomerically enriched guest solvent. ... 

NMR probe75. It is derived from d-norephedrine and may be used to derivatize chiral acids and determine optical purities of asymmetric centers as far away as nine atoms from the selenium atom12. 

Chiral separation by HPLC is a practically useful method not only for determining optical purity but also for obtaining optical isomers, and numerous CSPs are presently on the market. In order to achieve the efficient resolution of chiral compounds, we have to choose a suitable chiral column and eluent. The polysaccharide-based CSPs have a high chiral recognition ability and offer a high possibility for the successful resolution of racemates including aliphatic and aromatic compounds with or without functional groups under normal and reversed-phase conditions. 

Polarimetry coupled to a liquid chromatograph has been used to determine the optical purity of drugs [113-121]. The advantages of this approach for determining optical purity is that the enantiomers do not need to be resolved and only eluates which give rise to optical rotation or circular dichro-ism are detected. This advantage makes on-line polarimetry inherently more accurate than conventional polarimetry because minor interfering compo-... 

Racemic V could not be resolved with primary optically active bases presumably because they reacted in a Michael fashion. Formation of the quinine salt and five recrystallizations from a benzene/hexane mixture yielded an acid (after hydrolysis) whose specific rotation was [a]jP -47°. However, since the maximum specific rotation is unknown, an absolute method of determining optical purity is needed. The usual method is treatment with an optically pure derivatizing reagent to form covalent diastereo-mers, whose ratio can be determined by NMR or chromatography. 

In Table A-2, a selection of chiral organic solvents is given, together with some physical data. Such chiral solvents have received much attention because of their use in determining optical purities [9, 134], as media for stereoselective syntheses [10-12, 135, 136], and as NMR shift reagents [13]. 

Once again, the ratio of diastereomers is the same as that of the original enantiomers. High-pressure liquid chromatography has been used in a similar manner and has wider applicability. The direct separation of enantiomers by gas or liquid chromatography on a chiral column has also been used to determine optical purity. " Other methods... 

The arsino-anilines 53-61 were resolved by the fractional crystallization of (-1-)-hydrogentartrate salts (Table 3) . A handicap in evaluating the work relating to the resolution of the compounds 36-61 is the lack of experimental detail, and some inconsistencies in the physical data reported, together with the failure to determine optical purities and absolute configurations. 

Q8.3 Why is it important to convert your metal complex from the tartrate salt to a halide salt for determining optical purity ... 

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... 

Optical yields were assessed by transforming the hydrolyzed product (citronellal) via isopulegol into menthol which serves as a reliable reference substance for determining optical purity by specific rotation. 

In order to determine optical purity, it is necessary to know [tto]. In natural product synthesis, the rotation of the target is usually known, but the original authors may not have established that the isolated material was enantiomerically and chemically pure. One course of action is to resolve a sample and measure [ad yourself. This may prove tedious, but it has the advantage of eliminating any ambiguities between sample and standard. Another possibility is to calculate [tto] by isotopic dilution or kinetic resolution. 

The methods described in Section 6.9 are very useful for determining optical purities (enantiomeric excesses), but it is usually not possible to determine with certainty the absolute configuration of the major enantiomer present unless one has access to authentic samples of each pure enantiomer. This is rarely the case in natural product isolation or synthesis research. In 1973, Mosher described a method... 

Chiral nmr shift reagent and resolving agent. Reagent for determining optical purity of alcohols and amines. 

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