R/S Nomenclature of Enantiomers

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Enantiomers

One type of steorisomerism is that of optical isomers, also called enantiomers. Enantiomers are non-superimposable mirror-image pairs of stereoisomers, that is, a chiral molecule and its mirror image. This poses as problem for naming the compounds. Two enantiomers have the same atoms connected in the same way, so that following IUPAC nomenclature rules will give both compounds the same name. How can we distinguish the two mirror-images?

In organic chemistry, the most common origin of chirality is a tetrahedral (sp3) carbon atom bound to four different groups. A system of nomenclature to distinguish the two groups must somehow describe the three-dimensional arrangement of those four groups about the chiral carbon centre. This can be accomplished by ranking the four groups in decreasing order of priority, such that group a has the highest priority, followed by groups b, c, and d in decreasing order. The molecule is turned so that the group with the lowest rank (d) is behind the carbon atom, and the other three ranked groups form a wheel about the carbon. The ranking either forms a clockwise or counter-clockwise circle, tracing a path from a to b to c. If the path is clockwise, then the molecule is the R (rectus, right) enantiomer; if the path is counter-clockwise, the molecule is the S (sinister, left) enantiomer.

  a
  b
  c
  d
Place the lowest-priority group d behind the carbon.
Other groups form a clockwise path from a to b to c.
This is the R isomer.
  Place the lowest-priority group d behind the carbon.
Other groups form a counter-clockwise path from a to b to c.
This is the S isomer.

Cahn-Ingold-Prelog Rules

  1. Substituents are ranked according the atomic number of the atom connected to the chiral carbon, such that the atom with the higher atomic number gets higher priority. As a result, a hydrogen group is always lowest priority.
    Example: Cl (Z = 17) > O (Z = 8) > C (Z = 6) > H (Z = 1).


  2. If two substituents connected to the chiral carbon have the same priority, the atoms on the substituent chains are ranked at the first point of difference between the two chains. The group with atoms of greater atomic number at that point has higher rank. Note that the ranking is made only at the first point of difference on the chain. Atoms in the remainder of the chain are irrelevant.

    Example: -CH2CH2Br is ranked below -CH(OH)CH3, because the O atom on the second carbon gives this group higher priority. The presence of a Br group farther down the chain of the first group is irrelevant.


  3. Double and triple bonds are ranked as if the atom were connected to two or three different atoms of the same atomic number.

    Example: -CH=CH2 is treated as if each of the carbon atoms were connected to two different carbons, one for each of the C-C bonds. The atoms in red are not actually present, but are imagined for the purposes of assigning priority to the group. Thus, -C(=O)H has priority over the -CH(OH)CH3 group shown above, because the carbon in -C(=O)H is treated as if it had bonds to O, O, and H, which has greater priority than the first carbon in -CH(OH)CH3, with bonds to O, C, and H.

Practice Examples

For each of the chiral molecules below, determine whether the compound is the R or S isomer, as follows:

  1. Find the chiral carbon and identify and rank the four different groups around it
  2. Manipulate the molecule so that the lowest ranking group is at the back of the molecule.
  3. Determine whether the high-to-low ranking order forms a clockwise (R) or counter-clockwise (S) loop about the carbon.

1-chloro-1-fluoroethane
  1. Rankings: -Cl > -F > -CH3 > -H
  2. H is positioned in back
  3. Cl > F > CH3 wheel is counter-clockwise: S
4-cyano-2-butanol
  1. Rankings: -OH > -CH2CH2CN > -CH3 > -H
  2. H is positioned in back
  3. OH > CH2CH2CN > CH3 wheel is clockwise: R
4-hydroxy-3,4-dimethyl-2-pentanone
  1. Rankings: -C(=O)CH3 > -C(OH)(CH3)2 > -CH3 > -H
  2. H is positioned in back
  3. C(=O)CH3 > C(OH)(CH3)2 > CH3 wheel is counter-clockwise: S



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