Achiral Versus Chiral Methods

Stereoisomers are classified by symmetry as either enantiomers or diaste-reomers. Enantiomers have identical physical properties except for the direction of optical rotation. Diastereomers are basically stereoisomers that are not enantiomers of each other. A pair of enantiomers exists for all molecules containing a single chiral center and have the opposite configuration at each of the stereo centers. The maximum number of stereoisomers for a compound with n stereo centers is T. Diastereomers, on the other hand, have the same configuration at one of the two centers and have the opposite configuration at the other. 

The separation of chiral compounds will be discussed in Chapter 22. However, the separation of diastereomers can be accomplished using achiral stationary phases. Another alternative is the use of chiral columns for the separation of diastereomers in either the reversed-phase or normal-phase mode. The use of achiral bonded phases without chiral additives, such as phenyl and alkyl bonded phases for the separation of diastereomeric pharmaceutical compounds, is acceptable. Different selectivities can be obtained by employing stationary phases containing varying functionalities (phenyl, polar embedded moieties). The effect of aqueous mobile-phase pH, temperature, and type of organic eluent (acetonitrile versus methanol) can also play a dramatic role on the separation selectivity of diastereomeric compounds. 

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To understand how this method of resolution works, let s see what happens when a racemic mixture of chiral acids, such as (+)- and (-)-lactic acids, reacts with an achiral amine base, such as methylamine, CH3NH2. Stereochemically, the situation is analogous to what happens when left and right hands (chiral) pick up a ball (achiral). Both left and right hands pick up the ball equally well, and the products—ball in right hand versus ball in left hand—are mirror images. In the same way, both ( H- and (-)-lactic acid react with methylamine equally... 

Working at different temperatures allows one to perform thermodynamic studies which, in some cases, can provide information on the chiral mechanism. Chromatographic methods give the enantiomer retention factors, k. It is relatively easy to measure the k factors at different temperatures. The slope and intercept of the Van t Hoff plots (Ln k versus T) contain, respectively, the enthalpy. A//, and entropy, A5, variations of each enantiomer-selector global (chiral + achiral) interaction. 

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