Section 3: Lecture-3

What did you learn in the last lecture?

You learned:

 Optical isomers and Enantiomers

 Enantiomers and chirality

What are you going to learn in this chapter?

 Racemic Mixture or Racemate and their Resolution

 Representation of Different Configurations.
 (R)- and (S)-Nomenclature

Racemic Mixture
A mixture of enantiomers in equal amounts is called racemic mixture or racemate.
The racemate is optically inactive because the optical rotation caused by one
enantiomer will be cancelled out by its non-superimposable mirror image. Such
mixtures are denoted by prefix (±). For example, the racemic mixture of lactic acid
will be written as (±)-lactic acid.
The two enantiomers in a racemate can be separated by physical and chemical
methods. The separation of enantiomers from a racemate is referred as resolution.
Configuration and (R)- (S)-Convention of Nomenclature
The three-dimensional arrangement of atoms or groups around a stereogenic/chiral
carbon is described as configuration. Enantiomers will, thus, have opposite
configurations. The nomenclature of different configuration is done by using the
Cahn-Ingold-Prelog rule regarding the priority of atoms or groups around the
stereocenter. Before describing this system, it would be appropriate for you to
understand how to represent the structures of chiral molecules. This is explained
below by taking lactic acid as an example.
 OH CO2H CO2H
CO2H H C OH (dashes): going behind the
HO C H plane of the paper
2-hydroxypropanoic acid CH3 CH3 (wedges): going above the
(lactic acid) mirror plane of the paper

The dash – wedge formula of lactic acid.

This was simplified by Emil Fischer using a two-dimensional way that is
called the Fischer Projection Formula. In this formula, carbon atom is not shown and
dashes and wedges are replaced with straight vertical and horizontal lines. The
crossing point of the vertical and horizontal line represents the carbon atom. The
vertical line leads the groups that project below the plane of the paper whereas the
horizontal line projects the groups above the plane of the paper.

CO2H CO2H
H OH HO H
CH3 CH3
mirror
The Fischer projection formula of lactic acid.
Another way of representation is perspective formula that is more common.
In this formula, two of the bonds are shown in the plane of the paper, one bond as
dashed line directing below the plane of the paper and the fourth bond as the wedged
bond forwarding towards the viewer. The dashed and wedged bonds must be
adjacent to each other and so the two line bonds in the plane of the paper. For
example, see below the two enantiomers of lactic acid.
CO2H CO2H

H CH3 H3C
HO H
OH
Perspective formula of lactic acid.
(R)- and (S)-Nomenclature of Enantiomers
Now a days R,S system of nomenclature is widely accepted to describe the
configuration of enantiomers. In this system, four groups attached to a chiral carbon
are prioritized as 1 (highest priority), 2, 3, and 4 (lowest priority) by the Cahn-
Ingold-Prelog rule.
The chiral carbon is then observed from the side opposite to the lowest priority group
(4). If the remaining three groups 1, 2, and 3 form a clockwise pattern, the
configuration is designated R (from the Latin rectus meaning “right”). If they are in
anticlockwise fashion, the configuration is designated as S (from the Latin sinister
meaning “left”).
2 2
3
4 3 4
1 1

1, 2, 3: clockwise (R) 1, 2, 3: anticlockwise (S)

2 2

priority 4 at the back

1 3 3 1

1, 2, 3: clockwise (R) 1, 2, 3: anticlockwise (S)

2
2
1 3
3 1
4 4
mirror

1, 2, 3: clockwise (R) 1, 2, 3: anticlockwise (S)

The four groups are prioritized using the following set of rules (just like E-Z system).
Rule 1.
The atoms directly attached to the stereogenic center are ranked according to atomic
number – the higher the atomic number, the higher the priority. If one of the four
groups is H atom it is always given the lowest priority (4), and the stereogenic/chiral
carbon is viewed looking down the C-H bond from C to H. For example, if a chiral
carbon is attached to a bromine atom, an oxygen atom, a hydrogen atom and a carbon
atom, the priority of atoms/groups will be as follows.
Br > O > C > H
1 2 3 4
Rule 2.
If two or more directly attached atoms are same, work outward from the
stereogenic/chiral carbon until a decision is reached. In the molecule shown below,
the priority of methyl and ethyl groups cannot be decided by comparing the 1 st atom
attached to stereogenic carbon because in both of them it is carbon atom that is
directly attached to the stereogenic carbon. On working outward, we see that the
ethyl group has higher priority than the methyl group because at the first point of
difference between the methyl and ethyl groups there is a carbon atom in the ethyl
group and a hydrogen atom in the methyl group.
CH3
CH2
H CH3
HO
Rule 3.
If a double or triple bond needs to be considered in determining the priority, the
atoms involved are treated as being duplicated or triplicated, respectively. See the
examples below.
 H H
C CH2 should be treated as C C H
H
C C

C C
C CH should be treated as C C H
C C

H
C O should be treated as C O
H
O C
Let’s assume that a vinyl group and an isopropyl group are attached to the
stereogenic carbon. The vinyl group will have priority over the isopropyl group
because at the first point of difference there is a carbon atom in the vinyl group but
a hydrogen atom in the isopropyl group.
H H
CH=CH2 should be treated as C C H high priority
C C
vinyl group
H
C H
CH H low priority
isopropyl group C H
H H

Suggested Activity
Determine the priority of atoms/groups on the chiral carbon of compounds for which
you made models in previous lecture.