Optical isomerism 4.
The designation of configuration
Obviously it is necessary to assign and name the stereocenters unambiguously in chiral molecules. The (+) and (-) (or the older d and l) designation is inappropriate as this only shows the direction of the rotation and one cannot deduce the relativ position of substituents from this
As the absolute configuration of molecules were unknown earlier, the dextrorotatory (i.e. (+)) form of glyceraldehyde was arbitrary assigned with the D (capital) prefix and with the following structure(Fisher convention):
Using an appropriate chemical conversion (which surely does not change the bonds to the central carbon) dextrorotatory D-(+)-glyceraldehyde could be converted to the levorotatory (-)-lactic acid, therefore it was named to D-(-)-lactic acid. This D/L designation system tells us about the relative configuration of the molecules, compared to the enantiomers of glyceraldehyde as the standard compounds. Compounds with the same relative configuration as (+)-glyceraldehyde are assigned the D prefix, and those with the relative configuration of (-)-glyceraldehyde are given the L prefix. In the case of simple compounds several rules were applied to trace back the relative configuration to glyceraldehyde, for example:
Notice that using the above drawing style, exchanging two substituents we get to the opposite optical isomer. Exchanging twice there is no change in the configuration.
This D/L sytem is inappropriate for the description of complicated molecules or even simple ones, if they do not follow certain rules. Even in the case of compounds with two chiral centres the notation was not consistent and uniform, for example:
The classical names of the isomers of ephedrine and threonine
Because of the weaknesses of the D/L system a new unambiguous and absolute system (without a referent compound) is now widely used: the Cahn-Ingold-Prelog (CIP) or R/S convention.
Sequence Rules for Specifying Configuration of the CIP convention:
- Prioritize the four directly attached atoms (substituents) around a chiral center according to their atomic numbers. The atom of higher atomic number takes precedence over an atom with a lower atomic number. Orient the chiral centre such that the lowest priority atom (substituent) is pointing away from the viewer. The other three atoms lie now on a "steering wheel".
- Rank and number the three atoms according to their atomic number. The highest becomes #1, followed by #2 and #3.
- Clockwise path of substituents 1-2-3: assign to R-isomer; counterclockwise path of the substituents: assign to S-isomer.
R-2-Butanol S-2-Butanol
- If the relative priorities cannot be determined, the secondary (or beta) atoms are to be compared, thus e.g.: ‑CH3 < ‑CH2CH3 < ‑CH(CH3)2 < ‑CH2OCH3 < ‑Cl < ‑Br, etc.
- In the case of double or triple bond, the connected atom is considered to be duplicated or triplicated (but these phantom atoms have lower priority than that of two real ones): ‑CH2OH < ‑CHO [= ‑CH(O‑)2] < ‑CH(OR)2.
Excercises
Assign a priority number to each substituent at the chiral carbon atom (highest 1... lowest 4).
Determine the configuration of the compounds:
L-Alanine
L-Cysteine
D-Glyceraldehyde
Dichloro-cyclopropane
Cyclobutane derivative
4-Methyl-cyclohexene
2-Chloropentane
3-Bromo-4-chloropentane
3-Bromo-4-chloro-pentane
Determine the R/S configurations of the chiral carbons of the four threonine isomers shown above. Redraw the molecule in the more feasible zig-zag form using dashed/wedged (up/down) bonds.
The cinchona alkaloids quinine and quinidine have four chiral atoms, of those the configurations at C-8 and C-9 are different: quinine 8S-9R, quinidine 8R-9S. Assign the structures A and B to quinine and quinidine.
