4.3: Absolute Configuration and the (R) and (S) System
- Page ID
- name chiral compounds using (R) & (S) nomenclature
USE YOUR MODELING KIT: Models assist in visualizing the structure. When using a model, make sure the lowest priority is pointing away from you. Then determine the direction from the highest priority substituent to the lowest: clockwise (R) or counterclockwise (S).
IF YOU DO NOT HAVE A MODELING KIT: remember that the dashes mean the bond is going into the screen and the wedges means that bond is coming out of the screen. If the lowest priority bond is not pointing to the back, mentally rotate it so that it is. However, it is very useful when learning organic chemistry to use models.
If you have a modeling kit use it as you read through this section and work the practice problems.
Introduction and the Cahn-Ingold-Prelog rules of Priority
To name the enantiomers of a compound unambiguously, their names must include the "handedness" of the molecule. The letters "R" and "S" are determined by applying the Cahn-Ingold-Prelog (CIP) rules. The optical activity (+/-) can also be communicated in the name, but must be empirically derived. There are also biochemical conventions for carbohydrates (sugars) and amino acids (the building blocks of proteins).
The method of unambiguously assigning the handedness of molecules was originated by three chemists: R.S. Cahn, C. Ingold, and V. Prelog and, as such, is also often called the Cahn-Ingold-Prelog rules. In addition to the CIP system, there are two ways of experimentally determining the absolute configuration of an enantiomer:
- X-ray diffraction analysis. Note that there is no correlation between the sign of rotation and the structure of a particular enantiomer.
- Chemical correlation with a molecule whose structure has already been determined via X-ray diffraction.
However, for non-laboratory purposes, it is beneficial to focus on the R/S system. The sign of optical rotation, although different for the two enantiomers of a chiral molecule,at the same temperature, cannot be used to establish the absolute configuration of an enantiomer; this is because the sign of optical rotation for a particular enantiomer may change when the temperature changes.
The Cahn-Ingold-Prelog rules of priority are based on the atomic numbers of the atoms of interest. For chirality, the atoms of interest are the atoms bonded to the chiral carbon.
- The atom with higher atomic number has higher priority (I > Br > Cl > S > P > F > O > N > C > H).
- When comparing isotopes, the atom with the higher mass number has higher priority [18O > 16O or 15N > 14N or 13C > 12C or T (3H) > D (2H) > H].
- When there is a tie in (2) above, establish relative priority by proceeding to the next atom(s) along the chain until the first difference is observed.
Multiple bonds are treated as if each bond of the multiple bond is bonded to a unique atom. For example, the ethenyl group (CH2=CH) has higher priority than the ethyl group (CH3CH2). The ethenyl carbon priority is "two" bonds to carbon atoms and one bond to a hydrogen atom compared with the ethyl carbon that has only one bond to a carbon atom and two bonds to two hydrogen atoms. Similarly, the carbon-carbon triple bond of acetylene would give it higher CIP priority than the ethenyl group as summarized below.
Stereocenters are labeled R or S
The "right hand" and "left hand" nomenclature is used to name the enantiomers of a chiral compound. The stereocenters are labeled as R or S.
Consider the diagram above on the left: a curved arrow is drawn counter-clockwise (c-cw) from the highest priority substituent (1) to the lowest priority substituent (4) in the S-configuration ("Sinister" → Latin= "left"). The counterclockwise direction can be recognized by the movement left when leaving the 12 o' clock position. Now consider the diagram above on the right where a curved arrow is drawn clockwise (cw) from the highest priority substituent (1) to the lowest priority substituent (4) in the R configuration ("Rectus" → Latin= "right"). The R or S is then added as a prefix, in parenthesis, to the name of the enantiomer of interest. A locator number is required if there is more than one chiral center. Otherwise, the person reading the name is expected to recognize the chiral center.
The two chiral compounds below are drawn to emphasize the chiral carbon with the full chemical name below each structure.
Absolute Configurations of Perspective Formulas
Chemists need a convenient way to distinguish one stereoisomer from another. The Cahn-Ingold-Prelog system is a set of rules that allows us to unambiguously define the stereochemical configuration of any stereocenter, using the designations 'R ’ (from the Latin rectus, meaning right-handed) or ' S ’ (from the Latin sinister, meaning left-handed).
The rules for this system of stereochemical nomenclature are, on the surface, fairly simple.