Polarimetry optical purity

Since the early times of stereochemistry, the phenomena related to chirality ( dis-symetrie moleculaire, as originally stated by Pasteur) have been treated or referred to as enantiomericaUy pure compounds. For a long time the measurement of specific rotations has been the only tool to evaluate the enantiomer distribution of an enantioimpure sample hence the expressions optical purity and optical antipodes. The usefulness of chiral assistance (natural products, circularly polarized light, etc.) for the preparation of optically active compounds, by either resolution or asymmetric synthesis, has been recognized by Pasteur, Le Bel, and van t Hoff. The first chiral auxiliaries selected for asymmetric synthesis were alkaloids such as quinine or some terpenes. Natural products with several asymmetric centers are usually enantiopure or close to 100% ee. With the necessity to devise new routes to enantiopure compounds, many simple or complex auxiliaries have been prepared from natural products or from resolved materials. Often the authors tried to get the highest enantiomeric excess values possible for the chiral auxiliaries before using them for asymmetric reactions. When a chiral reagent or catalyst could not be prepared enantiomericaUy pure, the enantiomeric excess (ee) of the product was assumed to be a minimum value or was corrected by the ee of the chiral auxiliary. The experimental data measured by polarimetry or spectroscopic methods are conveniently expressed by enantiomeric excess and enantiomeric... 

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-... 

Calculate specific rotations from polarimetry data, and use specific rotations to determine the optical purity and the enantiomeric excess of mixtures. 

Determination of OY The OY of the reaction was evaluated using the optical purity of the product determined by polarimetry. 

Then we changed over to the isomer allylic alcohol, to 3-methyl-2-buten-l-ol (prenol). Being a primary alcohol, it was smoothly epoxidized under both stoichiometric and catalytic Sharpless conditions. While the stoichiometric method provides only moderate yields as the dimethyl glycidol is fairly watersoluble, the catalytic method affords the double yield. The e.e. amounts to 90% in both cases. Optical purity and e.e. of the 3,3-dimethyl glycidol were determined by polarimetry and -NMR in the presence of chiral europium shift-reagent [22]. 

GC and polarimetry as above indicated optical purities comparable to those obtained from the single crystal runs. In most of the runs, (-)-7.1d was obtained. 

The separation of the enantiomorphous crystals of racemic sodium ammonium tartrate by Pasteur in 1848, and his observation that the two forms were optically active in solution, linked the concept of molecular chirality to optical activity [1]. When Emil Fischer began the first serious attempts at asymmetric synthesis in the latter 19th century, the polarimeter was the most reliable tool available to evaluate the results of an enantioselective reaction (by determination of optical purity), and it remained the primary tool for nearly 100 years. Only recently has analytical chemistry brought us to the point where we can say that polarimetry has been superceded as the primary method of analysis in asymmetric synthesis. 

The optical purity is usually, but not always, equal to enantiomer excess. In order for the two to be equal, it is necessary that there be no aggregation. It is possible, for example, that a homochiral or heterochiral dimer (see Glossary, Section 1.6, for definitions) would refract the circularly polarized light differently than the monomer (or each other). In 1968 [19] Krow and Hill showed that the specific rotation of (S)-2-ethyl-2-methylsuccinic acid (85% ee) varies markedly with concentration, and even changes from levorotatory to dextrorotatory upon dilution. In 1969 [20], Horeau followed up on Krow and Hill s observation, and showed that the optical purity (at constant concentration) and enantiomer excess of (5)-2-ethyl-2-methylsuccinic acid were unequal except when enantiomerically pure or completely racemic. This deviation from linearity is known as the Horeau effect, and its possible occurence should be remembered when determining enantiomeric purity by polarimetry. 

The optical rotations, particularly in the uv, of chiral centers of R CHD)R are sufficiently large that it is practical to use polarimetry to measure optical purity. Generally, however, a sequence of steps to produce a known configuration organic product from a known configuration substrate is required, since the chiroptical properties of the metal complexes are not known. For example, the sequence of predominate inversion in oxidative addition and retention in carbonyl insertion has been investigated using Ph(CHD)Cl, Equation 44 R =... 

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. 

Due to the presence of some methylene chloride in the sample of the chiral amine, you may obtain low rotation values from polarimetry. Because of this, your calculated value of the optical purity (enantiomeric excess) and percentages of the enantiomers will be in error. The percentages of the enantiomers obtained from the optional chiral gas chromatography experiment below should provide more accurate percentages of each of the stereoisomers. 

The instructor may ask you to combine your remaining resolved naproxen with other students for determining the rotation of your (S)-naproxen by polarimetry. If so, your instructor will supply instructions. (S)-Naproxen has an observed specific rotation of +66°. The solvent, chloroform, will be used as the solvent, unless you are told otherwise. Calculate the % optical purity (% enantiomeric excess) for your sample and compare the results with the chiral HPLC results. Remember that the sample may only contain about 82% of the (S) enantiomers (Technique 23, Section 23.5) so you will not obtain a value of +66° from the polarimeter. 

What are the advantages of using a chiral shift reagent instead of polarimetry to determine the optical purity of a sample ... 

Traditionally and even today, polarimetry is used in many laboratories for control of optical purity. However, this method suffers from some well-known specific drawbacks. Furthermore, often calculation of the enantiomeric excess from optical rotation is impossible, because the specific rotation of the pure enantiomer is not known precisely, or calculated enantiomeric excess values may be wrong owing to impurities. For these reasons direct chromatographic analytical procedures are preferred. 

A few examples are known in which the optical purity and the enantiomeric excess are not equivalent. It is in any case generally advisable to determine e.e. by an independent method in addition to polarimetry (see chapter 3). 

In addition to requiring large sample sizes, high purity of the compound is an indispensible requirement in polarimetry. Chiral and achiral impurities may change the value of the optical... 

Optical rotation measurements are most commonly used to confirm the enantiomeric identities of resolved enantiomers. When reference standards of totally resolved materials are available, polarimetry can be used to determine the enantiomeric purity of samples of defined composition. 

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