Reference: McMurry Ch 6 George et al Ch 3.3

Recap: Some isomers have already been encountered – constitutional isomers (eg 1-butene and 2-butene); conformational isomers (e.g. staggered and eclipsed forms of ethane) and diastereomers such as (Z)- and (E)-2-butene or cis- and trans-1,2-dimethylcyclobutane.

Conformational isomers are one type of stereoisomer which generally can not be separated from one another at room temperature. Another class is configurational isomers, which can be separated from one another, as interconversion requires breaking of bonds. There are two types of configurational isomers: diastereisomers and enantiomers. Enantiomers are non-superposable mirror images.

• Chiral molecules (optical isomers) can be identified in this way: when a molecule and its mirror image are not identical (not superposable) the substance is chiral
• A pair of molecules which are not identical but are mirror images of each other are called enantiomers
• Almost all of the physical and chemical properties of a pair of enantiomers are identical (melting point, boiling point, solubility etc.)

• A sp³ hybridised carbon atom has a tetrahedral arrangement of bonds about it
• In molecules where there are four different groups attached to one carbon centre, there are two non-superposable mirror images. Such a carbon atom is called a stereogenic centre and the molecule is said to be chiral.

 Example:

In molecules where there are not four different groups attached to a single carbon centre then any mirror image is identical to the original, just drawn in a different way.

Enantiomers differ only in (i) the way that they interact with other chiral molecules, (ii) the way that they interact with polarised light.

• A sample of one enantiomer of a pair will rotate the plane of polarised light in a clockwise direction (labeled (+)) and an equal amount of the other enantiomer will rotate the plane of light to the same extent in a counter-clockwise direction (labeled (-))
• Molecules which rotate plane polarised light are called optically active molecule
• It is not currently possible to predict the direction or the magnitude of optical rotation from the molecular structure

The absolute configuration of a stereogenic centre refers to the exact three-dimensional arrangement of the groups. The method for naming enantiomers is called the Cahn-Ingold-Prelog convention and is based on describing the relative positions of the substituents attached to a stereogenic centre. Each stereogenic carbon centre has four different groups attached and these must firstly be assigned a relative priority according to a set of priority rules. These are the same rules used when naming (Z) and (E) alkenes.

(i) Each of the atoms attached directly to the stereogenic centre is assigned a priority based on its atomic number : the higher the atomic number, the higher the priority.

e.g. Increasing order of priority: H < C < N < O < Cl < Br < I

(ii) If two of the atoms attached to the stereogenic centre are identical (e.g. –CH₃, -CH₂CH₃), then look to the next atoms away from the stereogenic centre. If the atoms at this point are still the same, then move further from the stereogenic centre (and so on) until the point of difference is found (there must be a point of difference somewhere for the molecule to be chiral). The group priority is then assigned based on the atomic numbers of the atoms at the first point of difference.

e.g. -CH₃ < -CH₂CH₃ < -CH(CH₃)₂ < -CH₂Cl < -CH₂Br

(iii) For the purposes of assigning group priorities, multiple bonds are expanded to be an equivalent number of single bonds attached to similar atoms. So a -CH=CH₂ group is considered as equivalent to -CH(-CH₂)₂

Rotate the molecule so the group of lowest priority is away from you. If going from the group of 1^st to 2^nd to 3^rd priority traces a clockwise direction, the stereogenic centre is assigned the R configuration. If the path traced out is an anticlockwise direction, the stereogenic centre is assigned the S configuration.

• A mixture that contains equal amounts of the two enantiomers is called a racemic mixture
• A racemic mixture shows no net optical rotation
• There is no direct connection between the configuration of a stereogenic centre (R or S) and the direction of rotation of plane polarised light (+ or -)

If the reaction begins with achiral starting materials and generates a compound that contains a stereogenic centre, then equal numbers of molecules with R- and S- configurations at that centre will be formed and the product must be a racemic mixture.

 Example: Treatment of 2-butanone with 1) NaBH₄ and 2) H⁺ /H₂O forms a racemic mixture or 2-butanol.

• If there are "n" stereogenic centres in a molecule, there are a maximum of 2ⁿ possible stereoisomers
• There are four possible isomers of a compound with two stereogenic centres

• Isomers A & B are mirror images and enantiomers. Similarly C & D are a mirror image pair and also enantiomers of one another
• Consider the relationship between A & C and also A & D – these are not mirror image pairs and so are diastereomers. Similarly the relationship between B & C and B & D is a diastereomeric one
• Diastereomers may be separated by the normal physical methods (e.g. distillation, recrystallisation, chromatography)
• A special case occurs when a molecules with 2 (or 4, or 6…) stereogenic centres possesses an internal plane of symmetry wherein one stereogenic centre is the mirror image of the other. In this case the mirror images are superposable, i.e. identical. Such compounds are called meso compounds
• The meso form is a diastereomer of either of the enantiomeric forms
• Example: Tartaric acid (2,3-dihydroxy-1,4-butanedicarboxylic acid) has two stereogenic centres (at C2 and C3). The two stereogenic centres have identical substituents and one of the possible stereoisomers of this compound has an internal mirror plane such that C2 is one mirror image of C3. This stereoisomer is called the meso isomer of tartaric acid. Despite the fact that meso compounds have stereogenic centres, they are optically inactive. This is because the rotation of plane polarised light by one stereogenic centre within the molecule is equal and opposite to the rotation caused by the other (mirror image) stereogenic centre, and the two effects cancel.

Questions on Isomers and Stereochemistry

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