Chapter 5

Stereochemistry

NEPHAR 109 Organic Chemistry

Assist.Prof. Banu Keşanlı
Chapter 5 1
Isomerism: Constitutional Isomers and
Stereoisomers
z Stereoisomers are isomers with the same
molecular formula and same connectivity of
atoms but different arrangement of atoms in
space

Chapter 5 2
¾ Example of Enantiomers : Lactic acid

H H

HO OH
H3C CO2H HO2C CH3
(+) Lactic Acid (-) Lactic Acid

¾ Example Diastereomers : cis and trans

double bond isomers

Chapter 5 3
 Enantiomers and Chiral Molecules

Î Chiral molecule
• Not superposable on its mirror image
• Can exist as a pair of enantiomers

Î Pair of enantiomers
• A chiral molecule and its mirror image

Î Achiral molecule
• Superposable on its mirror image

Chapter 5 4
Chiral and Achiral Molecules
• Although everything has a mirror image, mirror images
may or may not be superimposable.
• Some molecules are like hands. Left and right hands are
mirror images, but they are not identical, or
superimposable.

Chapter 5 5
• Other molecules are like
socks. Two socks from a pair
are mirror images that are
superimposable. A sock and
its mirror image are identical.
• A molecule or object that is
superimposable on its mirror
image is said to be achiral.
• A molecule or object that is
not superimposable on its
mirror image is said to be
chiral.

Chapter 5 6
 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

Chapter 5 7
 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 8
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

Chapter 5 9
Stereogenic Centers
• To locate a stereogenic center, examine each tetrahedral
carbon atom in a molecule, and look at the four groups—
not the four atoms—bonded to it.
• Always omit from consideration all C atoms that cannot
be tetrahedral stereogenic centers. These include
CH2 and CH3 groups
Any sp or sp2 hybridized C

Chapter 5 10
• Larger organic molecules can have two, three or even
hundreds of stereogenic centers.

Chapter 5 11
• We can now consider several molecules to determine
whether or not they are chiral.

Chapter 5 12
• The molecule labeled A and its mirror image labeled B
are not superimposable. No matter how you rotate A and
B, all the atoms never align. Thus, CHBrClF is a chiral
molecule, and A and B are different compounds.
• A and B are stereoisomers—specifically, they are
enantiomers.
• A carbon atom with four different groups is a tetrahedral
stereogenic center.

Chapter 5 13
• In general, a molecule with no stereogenic centers will
not be chiral. There are exceptions to this that will be
considered in Chapter 17.
• With one stereogenic center, a molecule will always be
chiral.
• With two or more stereogenic centers, a molecule may or
may not be chiral.
• Achiral molecules usually contain a plane of symmetry
but chiral molecules do not.
• A plane of symmetry is a mirror plane that cuts the
molecule in half, so that one half of the molecule is a
reflection of the other half.

Chapter 5 14
Chapter 5 15
Summary of the Basic Principles of Chirality:

• Everything has a mirror image. The fundamental

question is whether the molecule and its mirror image
are superimposable.
• If a molecule and its mirror image are not
superimposable, the molecule and its mirror image are
chiral.
• The terms stereogenic center and chiral molecule are
related but distinct. In general, a chiral molecule must
have one or more stereogenic centers.
• The presence of a plane of symmetry makes a molecule
achiral.

Chapter 5 16
Classify each of the following pairs as chiral or achiral.
a) CH3 CH3

CH3 H3C
Cl Br Cl
Br

b) CH3 CH3

Br Br
Cl Cl H
H

H
c) Br Br H

F F

Chapter 5 17
The Biological Importance of Chirality
ÎThe binding specificity of a chiral receptor
site for a chiral molecule is usually only
favorable in one way

Chapter 5 18
Tests for Chirality: Planes 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
ÎExample
2-chloropropane (a) has a plane of symmetry but
2-chlorobutane (b) does not

Chapter 5 19
 Nomenclature of Enantiomers:
The R,S System

z Also called the Cahn-Ingold-Prelog system

z The four groups attached to the stereogenic
carbon are assigned priorities from highest (a)
to lowest (d)
z Priorities are assigned as follows
¾Atoms directly attached to the stereogenic
center are compared
¾ Atoms with higher atomic number are
given higher priority
¾If priority cannot be assigned based on
directly attached atoms, the next layer of
atoms is examined
Chapter 5 20
Example

Chapter 5 21
z The molecule is rotated to put the lowest
priority group back
ÎIf the groups descend in priority (a,b then c)
in clockwise direction the enantiomer is R
ÎIf the groups descend in priority in
counterclockwise direction the enantiomer is
S

Chapter 5 22
Which group in each pair has the highest priority?
a) -CH3 or -CH2CH3

b) -I or -Br

c) -CH3Br or -CH2CH2Br

Chapter 5 23
Label each compound as R or S.
a) Cl

H
H3C Br

b) CH2Br

ClH2C
OH
H3C

Chapter 5 24
 Properties of Enantiomers:
Optical Activity

z Enantiomers have almost all identical physical

properties (melting point, boiling point,
density)

z However enantiomers rotate the plane of

plane-polarized light in equal but opposite
directions

Chapter 5 25
z The specific rotation of the two pure
enantiomers of 2-butanol are equal but
opposite

z There is no straightforward correlation

between the R,S designation of an enantiomer
and the direction [(+) or (-)]in which it rotates
plane polarized light
Chapter 5 26
• With achiral compounds, the light that exits the sample
tube remains unchanged. A compound that does not
change the plane of polarized light is said to be optically
inactive.

Chapter 5 27
• With chiral compounds, the plane of the polarized light is
rotated through an angle α. The angle α is measured in
degrees (°), and is called the observed rotation. A
compound that rotates polarized light is said to be optically
active.

Chapter 5 28
 Racemic mixture

¾ A 1:1 mixture of enantiomers

¾ No net optical rotation
¾ Often designated as (+)

Chapter 5 29
 The Synthesis of Chiral Molecules
Most chemical reactions which produce chiral
molecules produce them in racemic form

Chapter 5 30
 Molecules with More than One
Stereogenic Center

z The maximum number of stereoisomers

available will not exceed 2n, where n is equal to
the number of tetrahedral stereogenic centers

Chapter 5 31
z There are two pairs of enantiomers (1, 2) and
(3,4)
ÎEnantiomers are not easily separable so 1
and 2 cannot be separated from each other
z Diastereomers: stereoisomers which are not
mirror images of each other
ÎFor instance 1 and 3 or 1 and 4
ÎHave different physical properties and can
be separated

Chapter 5 32
z Meso Compound
achiral despite the presence of stereogenic
centers
Î Not optically active
Î Superposable on its mirror image
Î Has a plane of symmetry

Chapter 5 33
Example for Meso Compounds

Chapter 5 34
Which of the following are meso compounds?
a)

b)

Cl
c)
OH

Chapter 5 35
 Fischer Projection Formulas
z A 2-dimensional representation of chiral
molecules
ÎVertical lines represent bonds that project
behind the plane of the paper
ÎHorizontal lines represent bonds that project
out of the plane of the paper

Chapter 5 36
 The Stereochemistry of SN2 Reactions

ÎStereochemistry can be controlled in SN2

reactions
• Backside attack of nucleophile results in an
inversion of configuration

Chapter 5 37
The Stereochemistry of SN1 Reactions
ÎWhen the leaving group leaves from a
stereogenic center of an optically active
compound in an SN1 reaction, racemization
will occur
• This is because an achiral carbocation
intermediate is formed
Racemization: transformation of an optically
active compound to a racemic mixture

Chapter 5 38
 Relating Configurations through Reactions in
which No Bonds to the Stereogenic Carbon are
Broken
ÎA 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 39
Chemical Properties of Enantiomers
• Two enantiomers have exactly the same chemical properties except
for their reaction with chiral non-racemic reagents.
• Many drugs are chiral and often must react with a chiral receptor or
chiral enzyme to be effective. One enantiomer of a drug may
effectively treat a disease whereas its mirror image may be
ineffective or toxic.

Chapter 5 40
 Example of Importance of Enantiomers in Drugs

The two enantiomers of thalidomide:

(S)-thalidomide (R)-thalidomide

Thalidomide is racemic – it contains both left-

and right-handed isomers in amounts.
The (R) enantiomer is effective against
morning sickness. The (S) is teratogenic and
causes birth defects. Chapter 5 41