Enantiomeric relationship

Pure enantiomeric substances show rotations that are equal in magnitude but opposite in direction. Unequal mixtures of enantiomers rotate light in proportion 

The optical purity is numerically equivalent to the enantiomeric excess, which is defined as 

Crabbe, Top. Stereochem. 1, 93 (1967) C. Djerassi, Optical Rotatory Dispersion McGraw-Hill, New York, 1960 P. Crabbe, Optical Rotatory Dispersion and Circular Dichroism in Organic Chemistry, Holden Day, San Francisco, 1965 E. Charney, The Molecular Basis of Optical Activity. Optical Rotatory Dispersion and Circular Dichroism, Wiley, New York, 1979. 

Enantiomeric substances also show differential absorption of circularly polarized light. This is called circular dichroism and is quantitatively expressed as the molecular ellipticity, 

Compounds in which chirality is the result of one or more carbon atoms having four nonidentical substituents represent the largest class of chiral molecules. A molecule having a single carbon atom with four nonidentical ligands is chiral. Carbon atoms with four nonidentical ligands are referred to as asymmetric carbon atoms since the molecular environment at such a carbon atom possesses no element of symmetry. 2-Butanol is an example of a chiral molecule and exists as two nonsuperimposable mirror images. Carbon-2 is an asymmetric carbon. 

The molecular ellipticity is analogous to specific rotation in that two enantiomers have exactly opposite values of 6 at every wavelength. Two enantiomers will thus show CD spectra having opposite signs. A compound with several absorption bands may show both 

Enantiomers in which the chiral center is tetracoordinate carbon represent the largest class of chiral molecules, and the student is by now familiar with the fact that while 2-butanol is chiral, ethanol is not. Molecules that are not chiral are said to be achiral. The tetrahedral orientation of ligands to 5/ -carbon requires that when any two of the ligands are identical, the molecule is achiral conversely, when four nonidentical ligands are present, the molecule must be chiral. It is seen that with two identical substituents, the molecule has a plane of symmetry. A molecule with a plane 

For a more detailed description, see G. C. Barrett, in Elucidation of Organic Structures by Physical and Chemical Methods, Second Edition, Vol. IV, Part 1, K. W. Bentley and G. W. Kirby (eds.), Wiley-Interscience, New York, 1972, Chap. VIII. 

Crabbe, Top. Stereochem. 1,93 (1967) C. Djerassi, Optical Rotatory Dispersion, McGraw-Hill Book Company, New York, 1960. 

Unless otherwise stated, all optical rotations given in this book will correspond to that of the sodium D line, 589 nm. 

The plane defined by the three atoms C(2)-C(l)-(0) is a plane of symmetry. Below is an example of nonsuperimposable mirror images in a chiral molecule  

Enantiomers in which the chiral center is tetracoordinate represent the largest class of chiral molecules. Molecules that are not chiral are achiral. The tetrahedral 

The necessary criterion that an object not be superimposable on its mirror image can be met by compounds in which the chiral center is other than tetracoordinate carbon. Many such examples are known, including sulfoxides in which the substituents on sulfur are different. These molecules are nonplanar, with significant barriers to pyramidal inversion. 

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If two enantiomers are mixed together in equal amounts the result is a racemic mixture. We meet a number of enantiomeric items in daily life. The left hand, for example, is the mirror image of the right hand and they are not superimposable (see Figure 8.1). This becomes obvious if we try to put a right glove on a left hand. Similarly, a pair of shoes is an enantiomeric relationship while the stock in a shoe store constitutes a racemic mixture. 

Let us now differentiate between structures which are asymmetric and dissymmetric. The word asymmetric conveys the idea that the molecule is completely devoid of the elements of symmetry. Dissymmetric on the other hand means not completely devoid of elements of symmetry but possessing so few elements of symmetry that on the whole it will posses two structures which will be the mirror images of each other. Therefore to avoid confusion the term asymmetric is used to cover examples which rotate the plane polarized light. The two forms of an optically active compound are called enantiometers or enantiomorphs or optical antipodes. They are also said to have enantiomeric relationship to each other. 

There are two constitutional repeat units (Sec. l-2c) from a stereochemical viewpoint, one with R configuration for the stereocenter and the other with S configuration for the stereocenter (corresponding to la and lb). These are referred to as the two configurational base units and have an enantiomeric relationship [IUPAC, 1966, 1981, 1996]. 

The final dehydration reaction (MTPI, DMPU, 18 h) on the alcohol 105 produced (+)-PHB (81) in 79% yield. This substance proved to be identical to the natural product by comparison of the H and 13C NMR spectra, mobility on TLC, IR spectra, mass spectra, and UV spectra. Comparison of the CD spectra of the natural (-)-PHB (6) and the synthetic (+)-PHB (81) confirmed the expected enantiomeric relationship between these two products. 

Darvon, which is a painkiller. Its enantiomer, known as Novrad, is an anticough agent. Notice how the enantiomeric relationship between these two drugs extends beyond their chemical structures In Chapter 45 we will talk about other cases where two enantiomers have quite different biological effects. 

A fundamental subclassification is that of stereoisomers, which can be divided into enantiomers and diastereoisomers. Either two stereoisomers are related to each other as object and nonsuperimposable mirror image, or they are not. In the former case, they share an enantiomeric relationship. This implies that the molecules are dissymmetric (chiral), and chirality is the necessary and sufficient condition for the existence of enantiomers. An example of an enantiomeric relationship is illustrated in diagram III which shows the (R)- and (S)-enantiomers (see Section 4.b) of... 

Mislow [18] has proposed a classification of isomers based not on the bonding connectivity of atoms as above, but on the pairwise interactions of all atoms (bonded and nonbonded) in a molecule. The operation of comparison of all pairwise interactions is called isometry (for detailed explanations, see [19]). Isomers in which all corresponding pairwise interactions are identical are said to be isometric, and they are anisometric if this condition is not fulfilled. Isometric molecules may be superimposable, in which case they are identical (homomeric), or they may be nonsuperimposable, in which case they share an enantiomeric relationship. As regards anisometric molecules, they are categorized as diastereoisomers or constitutional isomers, depending on whether their constitution is identical or not. This discussion is schematically summarized in the lower half of Fig. 2. 

The quasi-enantiomeric relationship of the two parent alkaloid derivatives, which are actually diastereomers due to the different attachment of the ethyl group, allows the preparation of either antipode of the diol in high enantiomeric excess. 

The four stereoisomers can be divided as shown into two pairs of enantiomers, where the (R )-(S) and (S,S)-(9) stereoisomers are enantiomers of one another, and the (S,R)-(10) and (i ,5)-(ll) stereoisomers are also an enantiomeric pair. The stereoisomers that do not have an enantiomeric relationship to one another, such as (i ,i )-(8) and (JB,S)-(11) are known as diastereomers. Like enantiomers, these molecules are not superimposable on one another, but unlike enantiomers, they do not exhibit the same physical, chemical, and spectral characteristics. Thus, they have different melting/boiling points, lipid solubility. 

Rather than compute AG for eqn. 11 and AG for eqn. 12 to obtain AAG, recognize that the left hand sides of both equilibria are identical. This arises from an enantiomeric relationship where A = A in an unbound state (recall from above that enantiomers have identical properties in an achiral environment which, in this case, is the unbound state). Consequently one need only compute the energies of the two diastereomeric complexes to determine which analyte is more tightly bound to the CSP and, accordingly, has the longer retention time on the column. 

Each diastereoisomer can be isolated in a pure optically active form. They display quasi mirror image circular dichroism curves which illustrates the enantiomeric relationship between the tantalum asymmetric centers. 

In comparison to the hybrid squares [Pd(/ )-(+)-BINAP)(58)2] [OTfls (5.88) and [Pt (7 )-(+)-BINAP)(58)2][OTf]g (5.89), the all metal squares were formed in significantly greater diastereomeric excesses and were conformationally much more rigid. This was confirmed by VT H-NMR studies carried on these chiral squares with only metal corners. In brief the C2h-symmetrical connector ligands are locked into a chiral conformation in the square assemblies and must be restricted in rotation due to the presence of two - of just one - metal comers. As expected the use of the opposite chiral metallo-corners based on the (5)-(—)-BINAP ligand allowed the preparation of the opposite enantiomers of chiral molecular squares. The CD spectra of these chiral species confirmed the expected enantiomeric relationship. 

A different conformational picture is encountered when the eight-membered ring is fused with two aromatic rings as illustrated by the conformational analysis on the dibenzo[d ][l,3>6]dioxazocine (7) skeleton carried out by Farkas et al. <85JST131>. The possible structures can be divided into the quasi-rigid Q symmetric butterfly conformation (7a), which has the hetero ring in the crown conformation, and two flexible conformational families with an enantiomeric relationship... 

Let us consider two achiral stereoisomers (2 and 3) shown in Fig. 10.2. They are also stereoisomeric to 1 and 1 shown in Fig. 10.1. By the above definitions, the relationship between 1 and 2 (or 3) is concluded to be diastereomeric, because the enantiomer 1 is different to the achiral 2. On the other hand, the relationship between the achiral 2 and 3 is also concluded to be diastereomeric, because their mirror images (2 and 3 themselves) are different to each other. It should be noted, however, that the diastereomeric relationship between 1 and 2 is different from the diastereomeric relationship between 2 and 3 in whether there exist enantiomeric relationships or not. 

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