Chapter 5
Stereochemistry: Chiral Molecules
Chapter 5
Isomerism: Constitutional Isomers and
Stereoisomers
Stereoisomers are isomers with the same molecular
formula and same connectivity of atoms but different
arrangement of atoms in space
Chapter 5
Enantiomers: stereoisomers whose molecules are
nonsuperposable mirror images
Diastereomers: stereoisomers whose molecules are not
mirror images of each other
Example: cis and trans double bond isomers
Example: cis and trans cycloalkane isomers
Chapter 5
Enantiomers and Chiral Molecules
Chiral molecule
Not superposable on its mirror image
Can exist as a pair of enantiomers
Pair of enantiomers
A chiral molecule and its mirror image
Achiral molecule
Superposable on its mirror image
Chapter 5
Example: 2-butanol
I and II are mirror images of each other (figures a and b)
I and II are not superposable and so are enantiomers (figure c)
2-butanol is a chiral molecule
Example: 2-propanol
Not chiral
Chapter 5
Chiral molecule
A molecule with a single tetrahedral carbon bonded to four different groups will
always be chiral
A molecule with more than one tetrahedral carbon bonded to four different groups
is not always chiral
Switching two groups at the tetrahedral center leads to the enantiomeric molecule
in a molecule with one tetrahedral carbon
Stereogenic center
An atom bearing groups of such nature that an interchange of any two groups will
produce a stereoisomer
Carbons at a tetrahedral stereogenic center are designated with an asterisk (*)
Example: 2-butanol
Chapter 5
The Biological Importance of Chirality
The binding specificity of a chiral receptor site for a chiral
molecule is usually only favorable in one way
Chapter 5
Tests for Chirality: Planes of Symmetry
Plane of symmetry
An imaginary plane that bisects a molecule in such a way that the two halves of
the molecule are mirror images of each other
A molecule with a plane of symmetry cannot be chiral
Example
2-Chloropropane (a) has a plane of symmetry but 2-chlorobutane (b) does not
Chapter 5
Nomenclature of Enantiomers: The R,S System
Also called the Cahn-Ingold-Prelog system
The four groups attached to the stereogenic carbon are
assigned priorities from highest (a) to lowest (d)
Priorities are assigned as follows
Atoms directly attached to the stereogenic center are compared
Atoms with higher atomic number are given higher priority
If priority cannot be assigned based on directly attached atoms,
the next layer of atoms is examined
Example
Chapter 5
The molecule is rotated to put the lowest priority group
back
If the groups descend in priority (a,b then c) in clockwise direction
the enantiomer is R
If the groups descend in priority in counterclockwise direction the
enantiomer is S
Chapter 5
10
Groups with double or triple bonds are assigned
priorities as if their atoms were duplicated or triplicated
Chapter 5
11
Problem: Are A and B identical or enantiomers?
Manipulate B to see if it will become superposable with A
Exchange 2 groups to try to convert B into A
One exchange of groups leads to the enantiomer of B
Two exchanges of groups leads back to B
Chapter 5
12
Properties of Enantiomers: Optical Activity
Enantiomers have almost all identical physical
properties (melting point, boiling point, density)
However enantiomers rotate the plane of plane-polarized
light in equal but opposite directions
Plane polarized light
Oscillation of the electric field of ordinary light occurs in all
possible planes perpendicular to the direction of propagation
If the light is passed through a polarizer only one plane emerges
Chapter 5
13
The Polarimeter
Chapter 5
14
Specific Rotation
An empty sample tube or one containing an achiral molecule will
not rotate the plane-polarized light
An optically active substance (e.g. one pure enantiomer ) will
rotate the plane-polarized light
The amount the analyzer needs to be turned to permit light through is called the
observed rotation a
The standard value specific rotation [a] can be calculated
If the analyzer is rotated clockwise the rotation is (+) and the molecule is
dextrorotatory
If the analyzer is rotated counterclockwise the rotation is (-) and the molecule is
levorotatory
Chapter 5
15
The specific rotation of the two pure enantiomers of 2-
butanol are equal but opposite
There is no straightforward correlation between the R,S
designation of an enantiomer and the direction [(+) or
(-)]in which it rotates plane polarized light
Racemic mixture
A 1:1 mixture of enantiomers
No net optical rotation
Often designated as (+)
Chapter 5
16
Racemic Forms and Enantiomeric Excess
Often a mixture of enantiomers will be enriched in one
enantiomer
One can measure the enantiomeric excess (ee)
Example : The optical rotation of a sample of 2-butanol
is +6.76o. What is the enantiomeric excess?
Chapter 5
17
The Synthesis of Chiral Molecules
Most chemical reactions which produce chiral
molecules produce them in racemic form
Chapter 5
18
Molecules with More than One Stereogenic
Center
The maximum number of stereoisomers available will
not exceed 2n, where n is equal to the number of
tetrahedral stereogenic centers
Chapter 5
19
There are two pairs of enantiomers (1, 2) and (3,4)
Enantiomers are not easily separable so 1 and 2 cannot be
separated from each other
Diastereomers: stereoisomers which are not mirror
images of each other
For instance 1 and 3 or 1 and 4
Have different physical properties and can be separated
Chapter 5
20
Meso Compounds
Sometimes molecules with 2 or more stereogenic
centers will have less than the maximum amount of
stereoisomers
Chapter 5
21
Meso compound: achiral despite the presence of
stereogenic centers
Not optically active
Superposable on its mirror image
Has a plane of symmetry
Chapter 5
22
Naming Compounds with More than One
Stereogenic Center
The molecule is manipulated to allow assignment of
each stereogenic center separately
This compound is (2R, 3R)-2,3-dibromobutane
Chapter 5
23
Fischer Projection Formulas
A 2-dimensional representation of chiral molecules
Vertical lines represent bonds that project behind the plane of the
paper
Horizontal lines represent bonds that project out of the plane of
the paper
Chapter 5
24
Stereoisomerism of Cyclic Compounds
1,4-dimethylcyclohexane
Neither the cis not trans isomers is optically active
Each has a plane of symmetry
Chapter 5
25
1,3-dimethylcyclohexane
The trans and cis compounds each have two stereogenic centers
The cis compound has a plane of symmetry and is meso
The trans compound exists as a pair of enantiomers
Chapter 5
26
Relating Configurations through Reactions in
which No Bonds to the Stereogenic Carbon are
Broken
A reaction which takes place in a way that no bonds to the
stereogenic carbon are broken is said to proceed with retention of
configuration
Chapter 5
27
Relative configuration: the relationship between
comparable stereogenic centers in two different
molecules
(R)-1-Bromo-2-butanol and (S)-2-butanol have the same relative
configuration
Absolute configuration: the actual 3-dimensional
orientation of the atoms in a chiral molecule
Can be determined by x-ray crystallography
Chapter 5
28
Chiral Molecules that Do Not Possess a
Tetrahedral Atom with Four Different Groups
Atropoisomer: conformational isomers that are stable
Allenes: contain two consecutive double bonds
Chapter 5
29
