Enantiomers chemical properties

Stereochemistry (Chapter 7) Chemistry in three dimensions the relationship of physical and chemical properties to the spatial arrangement of the atoms in a molecule Stereoelectron ic effect (Section 5 16) An electronic effect that depends on the spatial arrangement between the or bitals of the electron donor and acceptor Stereoisomers (Section 3 11) Isomers with the same constitu tion but that differ in respect to the arrangement of their atoms in space Stereoisomers may be either enantiomers or diastereomers... 

Enantiomers. Two nonsuperimposable structures that are mirror images of each other are known as enantiomers. Enantiomers are related to each other in the same way that a right hand is related to a left hand. Except for the direction in which they rotate the plane of polarized light, enantiomers are identical in all physical properties. Enantiomers have identical chemical properties except in their reactivity toward optically active reagents. 

Multiple Chiral Centers. The number of stereoisomers increases rapidly with an increase in the number of chiral centers in a molecule. A molecule possessing two chiral atoms should have four optical isomers, that is, four structures consisting of two pairs of enantiomers. However, if a compound has two chiral centers but both centers have the same four substituents attached, the total number of isomers is three rather than four. One isomer of such a compound is not chiral because it is identical with its mirror image it has an internal mirror plane. This is an example of a diaster-eomer. The achiral structure is denoted as a meso compound. Diastereomers have different physical and chemical properties from the optically active enantiomers. Recognition of a plane of symmetry is usually the easiest way to detect a meso compound. The stereoisomers of tartaric acid are examples of compounds with multiple chiral centers (see Fig. 1.14), and one of its isomers is a meso compound. 

There are interesting examples of enantiomers that not only are found separately but also have different chemical properties when reacting with some reagent which is itself an enantiomer. For example (+ )-glucose is metabolized by animals and can be fermented by yeasts, but (—)-glucose has neither of these properties. The enantiomer ( + )-carvone smells of caraway whereas (—)-carvone smells of spearmint. 

Traditionally, chiral separations have been considered among the most difficult of all separations. Conventional separation techniques, such as distillation, Hquid—Hquid extraction, or even some forms of chromatography, are usually based on differences in analyte solubiUties or vapor pressures. However, in an achiral environment, enantiomers or optical isomers have identical physical and chemical properties. The general approach, then, is to create a "chiral environment" to achieve the desired chiral separation and requires chiral analyte—chiral selector interactions with more specificity than is obtainable with conventional techniques. 

Chemical Properties. Because of its chiral center, malic acid is optically active. In 1896, when tartaric acid was first reduced to malic acid, the levorotatory enantiomer, S(—), was confirmed as having the spatial configuration (1) (5,6). The other enantiomer (2) has the R configuration. A detailed discussion of configuration assignment by the sequence rule or the R and S system is available (7). 

Chemical Properties. The notation used by Chemical Abstracts to reflect the configuration of tartaric acid is as follows (R-R, R )-tartaric acid [S7-69A-] (4) (S-R, R )-tartaric acid [147-71-7] (5) and y j O-tartaric acid [147-73-9] (6). Racemic acid is an equimolar mixture of the two optically active enantiomers and, hence, like the meso acid, is optically inactive. 

Discrimination between the enantiomers of a racemic mixture is a complex task in analytical sciences. Because enantiomers differ only in their structural orientation, and not in their physico-chemical properties, separation can only be achieved within an environment which is unichiral. Unichiral means that a counterpart of the race-mate to be separated consists of a pure enantiomeric form, or shows at least enrichment in one isomeric form. Discrimination or separation can be performed by a wide variety of adsorption techniques, e.g. chromatography in different modes and electrophoresis. As explained above, the enantioseparation of a racemate requires a non-racemic counterpart, and this can be presented in three different ways ... 

The deoxyinositols (quercitols, cyclohexanepentols) are useful model compounds which display many of the physical and chemical properties of true deoxy sugars. Although (-b)-proto-quercitol, the best known isomer, was isolated from nature 118 years ago, no synthesis has been reported up until now. The synthesis here described is actually that of the (-)-enantiomer, starting with (-)-inositol however, identical procedures applied to the readily available ( + ) or dl-inositol would give (- -) or DL-proto-quercitol, respectively. The natural occurence of, )-proto-quercitol has... 

Enantiomers have identical chemical properties, except when they react with other chiral compounds. Because many biochemical substances are chiral, one consequence of this difference in reactivity is that enantiomers may have different odors and pharmacological activities. The molecule has to fit into a cavity, or slot, of a certain shape, either in an odor receptor in the nose or in an enzyme. Only one member of the enantiomeric pair may be able to fit. 

If a molecule is nonsuperimposable on its miixor image, the mirror image must be a different molecule, since superimposability is the same as identity. In each case of optical activity of a pure compound there are two and only two isomers, called enantiomers (sometimes enantiomorphs), which differ in structure only in the left-and right-handedness of their orientations (Fig. 4.1). Enantiomers have identical physical and chemical properties except in two important respects ... 

Most methods for the resolution of enantiomers contained in a reaction mixture consist in the conversion of the compounds into stable or transient diastereoisomers and separation of the latter on the basis of their different physico-chemical properties. 

Enantiomers have structures of exactly the same kind and yet are different. Their structures correspond to mirror images. In their physical properties they differ only with respect to phenomena that are polar, i.e. that have some kind of a preferred direction. This especially includes polarized light, the polarization plane of which experiences a rotation when it passes through a solution of the substance. For this reason enantiomers have also been called optical isomers. In their chemical properties enantiomers differ only when they react with a compound that is an enantiomer itself. 

Moving on to some wider stereochemical considerations, just as enantiomers are indistinguishable as far as their physical and chemical properties are concerned (except, of course, as regards their reactions with other optically active reagents) so their spectra, acquired under normal conditions, are identical. The NMR spectrometer does not differentiate between optically pure samples and racemic ones. Note there is a way of differentiating between enantiomers by NMR but it involves using certain chiral reagents which we ll discuss in detail later. 

Optical isomerism is exhibited by compounds that are chiral, i.e., are not superimposable on their mirror images. Such a compound and its mirror image are called optical isomers or enantiomers. They have identical physical and chemical properties except when they interact with other chiral molecules. 

Unlike enantiomers, diastereoisomers have similar but not identical chemical properties. The enantiomers have identical properties except the reactions with dissymmetric reagents. 

Another aspect of the chemical properties of mixmres of enantiomers has been reported by Wynberg and Feringa in 1976. These authors have smdied some dia-stereoselective reactions on chiral molecules (such as the LiAlH4 reduction of camphor) in the absence of chiral auxiliaries. They found that the product distribution was significantly different if the substrate was enantiopure or racemic. Similarly, it is known that reduction of enantiopure or racemic camphor by K/liquid NH3 gives rise to different isobomeol/bomeol ratios, a detailed mechanistic analysis has been done by Rautenstrauch. °... 

Enantiomers have very similar chemical properties, but they rotate polarized light in opposite directions (optical activity, see pp. 36,58). The same applies to the enantiomers of lactic acid. The dextrorotatory L-lactic acid occurs in animal muscle and blood, while the D form produced by microorganisms is found in milk products, for example (see p.l48). The Fischer projection is often used to represent the formulas for chiral centers (cf.p. 58). 

The inherent difficulty in analyzing enantiomers arises from the well-known fact that apart from their chiroptical characteristics, optical isomers have identical physical and chemical properties in an achiral environment (assuming ideal conditions). Therefore, methods of distinguishing enantiomers must rely on either their chiroptical properties (optical rotation, optical rotatory dispersion, circular dichroism), or must employ a chiral environment via diastereomer formation or interaction. Recently, it has become increasingly clear that such diastereomeric relationships may already exist in nonracemic mixtures of enantiomers via self-association in the absence of a chiral auxiliary (see Section 3.1.4.7.). 

Problem 5.19 Compare physical and chemical properties of (a) enantiomers, (h) an enantiomer and its racemic form, and (c) diastereomers. 

Properties of enantiomers Enantiomers share same physical properties, e.g. melting points, boiling points and solubilities. They also have same chemical properties. However, they differ in their activities with plane polarized light, which gives rise to optical isomerism, and also in their pharmacological actions. 

In some cases, physical and chemical properties are highly predictive of toxicity. A good example is acute aquatic toxicity, which is discussed in detail later in this chapter. However, some biological interactions that lead to toxicity, such as receptor binding, are highly specific and in those cases it is less likely that straightforward relationships between properties and toxicity can be found. A common example is the difference in toxicity of two enantiomers, such as the R- and S-enantiomers of thalidomide. 

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