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Introduction
Stereochemistry stems from the idea that molecules are not two-dimensional structures that we see on a page; instead, they are three-dimensional structures. When a molecule is planar, it lies in a single plane, and can be regarded as ‘two-dimensional’ for our purposes (note that the molecule is still three-dimensional in reality since atoms have diameters). When a molecule lies in more than one plane, it is no longer planar and can be regarded as ‘three-dimensional’ for our purposes. The issue we must contend with in stereochemistry is of two molecules, which have the same arrangement of atoms, and are effectively isomers of each other, completely the same in a two-dimensional respect. However, when we look at the two molecules three-dimensionally, we find that one of the molecules has a substituent pointing towards the plane of the page (and toward the reader) while the other molecule has the same substituent pointing away from the reader. This orientation of substituents in molecules is the basis of stereochemistry.
When isomeric molecules differ simply by the orientation of their substituents in a three-dimensional space, they are known as stereoisomers. It is not always possible for stereoisomers to exist for every molecule. To have a stereoisomer, the molecule’s mirror image (i.e. its stereoisomer) must not be superimposable on it (Fig. 1), because if there is superimposability, the molecule’s mirror image will be exactly the same as it, and it will not have stereoisomers. Generally, molecules with chiral centers, also known as stereocenters, will have stereoisomers, although there are exceptions to this, as we will learn about later. The chiral center refers to a chiral atom (usually only carbon is important for undergraduate organic chemistry) which is bonded to four chemically different groups. Note here that we state ‘groups’, not ‘atoms’; as such, a CH3 group and a CH3CH3 group are considered chemically different. Even isotopic differences matter; a deuterium atom is chemically different from a hydrogen atom. To indicate a chiral center, an asterisk (*) as seen in Fig. 1 is used. All stereoisomers have a chiral center.
Fig. 1: Superimposability of mirror images suggests chirality.
To prove whether a molecule has a chiral center and is chiral empirically, simply obtain mixtures of both stereoisomers and shine plane-polarized light (light that points in one plane) at them; they should rotate this plane-polarized light.
Enantiomers
When two molecules rotate plane-polarized light in different directions, they are known as enantiomers (Fig. 2); the molecule that rotates plane-polarized light to the right, it is a dextro isomer and given the (+) expression in front of its name. Where it rotates plane-polarized light to the left, it is a levo isomer and given the (-) expression in front of its name. Enantiomers are mirror images of each other, but although they simply differ in the orientation of their substituent chains (on the chiral centers), they react at different rates with other chiral centers, and the rates can vary greatly; from almost negligible to being highly significant. A commonly cited ‘application’ of this is in drug discovery, where a molecule may not be a very strong drug, but its stereoisomer may be highly biologically active and potent. Other than other chiral reactants, the effect cited above is also observed with chiral catalysts which participate in the reaction as well.
Fig. 2: Structure of enantiomers.
When equimolar amounts of two enantiomers exist as a mixture, it is termed a racemic mixture. The properties of this mixture are interesting; since the enantiomers ‘cancel’ each other out, it will not rotate plane-polarized light. Furthermore, the racemic mixture will have different properties than each of the enantiomers, notably, the melting and boiling points will be different.
Meso Compounds
Chiral carbons are arguably not reliable indicators of chiral molecules; there are some molecules which have chiral carbon centers, but yet do not have a stereoisomer. Such molecules are meso, and form meso compounds (Fig. 3). The reason why meso compounds lack a stereoisomer is because they are symmetrical (they have a plane of symmetry); therefore, even though they have chiral centers, they are superimposable on their mirror images, and therefore cannot rotate plane-polarized light. If a molecule has both a plane of symmetry and a chiral center, the chiral center should be reflected across the plane of symmetry. As such, a compound which has only one chiral center should be chiral. Furthermore, it is not possible for the chiral center to be exactly on the plane of symmetry as that would mean its substituents would be reflected across making it nonchiral. In the end, the ‘ultimate’ test of chirality for all compounds is not whether a chiral center is present on its molecules, but rather whether it rotates plane-polarized light.
Fig. 3: Structure of meso compounds.
Stereocenters
Stereocenters, or chiral centers, are one possible indicator of optically active compounds (which have enantiomers), although not always, as we have seen. As we already know, for carbons to be chiral, they have to be bonded to four chemically different substituents. Now we will take a look at some other atoms that are still chiral but are not carbons. Firstly, other atoms that are quadrivalent (form four bonds) like carbon are also chiral if they form four bonds to four chemically different substituents. For instance, such atoms include silicon (and other Group 14 members) as well as even nitrogen (which sometimes forms four bonds, notably in ammonium salts) can be chiral as long as they are bonded to four chemically different substituents. Tervalent atoms can also be stereocenters if they bond to three chemically different substituents, but a requirement is that the geometry about this atom has to be pyramidal. Most secondary and tertiary amines undergo pyramidal inversion, however, rapidly converting them into their enantiomers.
In the next part (released on Wednesday), more examples of stereocenters and chiral compounds will be discussed.