Enantiomer physical

Specific rotation is a physical property of a substance just as melting point boil mg point density and solubility are For example the lactic acid obtained from milk is exclusively a single enantiomer We cite its specific rotation m the form [a]o =+3 8° The temperature m degrees Celsius and the wavelength of light at which the measure ment was made are indicated as superscripts and subscripts respectively... 

The usual physical properties such as density melting point and boiling point are iden tical for both enantiomers of a chiral compound... 

Section 7 4 Optical activity, or the degree to which a substance rotates the plane of polarized light is a physical property used to characterize chiral sub stances Enantiomers have equal and opposite optical rotations To be optically active a substance must be chiral and one enantiomer must be present m excess of the other A racemic mixture is optically inactive and contains equal quantities of enantiomers... 

Section 7 8 Both enantiomers of the same substance are identical m most of then-physical properties The most prominent differences are biological ones such as taste and odor m which the substance interacts with a chiral receptor site m a living system Enantiomers also have important conse quences m medicine m which the two enantiomeric forms of a drug can have much different effects on a patient... 

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. 

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. 

When additional substituents ate bonded to other ahcycHc carbons, geometric isomers result. Table 2 fists primary (1°), secondary (2°), and tertiary (3°) amine derivatives of cyclohexane and includes CAS Registry Numbers for cis and trans isomers of the 2-, 3-, and 4-methylcyclohexylamines in addition to identification of the isomer mixtures usually sold commercially. For the 1,2- and 1,3-isomers, the racemic mixture of optical isomers is specified ultimate identification by CAS Registry Number is fisted for the (+) and (—) enantiomers of /n t-2-methylcyclohexylamine. The 1,4-isomer has a plane of symmetry and hence no chiral centers and no stereoisomers. The methylcyclohexylamine geometric isomers have different physical properties and are interconvertible by dehydrogenation—hydrogenation through the imine. 

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

Crystallization methods are widely used for the separation, or resolution, of enantiomer pairs. Enantiomer mixtures may essentially crystallize in two different ways. In around 8 per cent of cases, each enantiomer crystallizes separately, giving rise to a mechanical mixture of crystals of the two forms, known as a conglomerate. Conglomerates may usually be separated by physical methods... 

Now, consider the physical properties of these stereoisomers. Enantiomers should have many of the same physical properties, such as energy and dipole moment, but diastereomers should not. Obtain the energy of each conformer and use equation (1) to calculate the composition of a large sample of each stereoisomer at 298 K. Then, obtain the dipole moment of each conformer and use equatiori (2) to calculate the dipole moment of a large sample of each stereoisomer at 298 K. Do enantiomers have the same dipole moment Do diastereomers have different dipole moments ... 

Process validation should be extended to those steps determined to be critical to the quality and purity of the enantiopure drug. Establishing impurity profiles is an important aspect of process validation. One should consider chemical purity, enantiomeric excess by quantitative assays for impurity profiles, physical characteristics such as particle size, polymorphic forms, moisture and solvent content, and homogeneity. In principle, the SMB process validation should provide conclusive evidence that the levels of contaminants (chemical impurities, enantioenrichment of unwanted enantiomer) is reduced as processing proceeds during the purification process. 

There are circumstances in which it is not possible to obtain the required enantiomer at manufacturing scale either by synthesis or isolation, e.g. because of difficulties with scale-up or failure to obtain material in a suitable physical form for pharmaceutical manufacture. In such cases, all the experimental results available should be described and the reason for the failure given. Likewise, if enantiomeric material could not be obtained for preclinical and clinical studies (see below), this should also be discussed. Advances in preparative techniques should eventually make this scenario less common. 

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... 

Today, we would describe Pasteur s work by saying that he had discovered enantiomers. Enantiomers, also called optical isomers, have identical physical properties, such as melting point and boiling point, but differ in the direction in which their solutions rotate plane-polarized light. 

Although the different enantiomers of a chiral molecule have the same physical properties, they usually have different biological properties. For example, the (+) enantiomer of limonene has the odor of oranges, but the (-) enantiomer has the odor of pine trees. 

Meso compounds contain chirality centers but are achiral overall because they have a plane of symmetry. Racemic mixtures, or racemates, are 50 50 mixtures of (+) and (-) enantiomers. Racemic mixtures and individual diastereomers differ in their physical properties, such as solubility, melting point, and boiling point. 

Except for their effect on plane-polarized light, two enantiomers of a chiral compound have identical physical properties. For example, the two isomers of lactic acid shown below have the same melting point, 52°C, and density, 1.25 g/mL. 

A chiral complex is one that is not identical to its mirror image. Thus, all optical isomers are chiral. The cis isomers of [CoCl2(en)2 + are chiral, and a chiral complex and its mirror image form a pair of enantiomers. The trans isomer is superimposable on its mirror image complexes with this property are called achiral. Enantiomers differ in one physical property chiral molecules display... 

Enantiomers differ in one physical property chiral molecules display optical activity, the ability to rotate the plane of polarization of light (Section 16.7 and Box 16.2). If a chiral molecule rotates the plane of polarization clockwise, then its mirror-image partner rotates it through the same angle in the opposite direction. 

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 ... 

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