Stereoisomerism

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 Outline
• Isomerism
• Divisions of Isomers (Constitutional and
Stereoisomer)
• Types of Stereoisomers (Enantiomers and
Diastereomers)
• Types of Geometric Isomers (Cis and
Trans)
• Optical Isomers
• Meso Compound and Racemic Mixtures 2
Isomerism

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 Molecular formula: C4H10
H
H H H H H H
H C H
H C C C C H
H C C C H
H H H H

butane or n-butane H H H
bp = -0.5 C isobutane
mp = -138.3 C bp = -11.7 C
mp = -159.5 C
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Figure 19.8 Ball-and-stick models illustrating
structural formulas of butane and isobutane.

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Isomers
- compounds that have the same
molecular formula, but different
arrangement of atoms in space.
- the same number and kind of
atoms
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 Isomers
• Recognizing the difference between
isomers is fundamental not only for
classification but also because they can
differ in chemical and biological
properties.

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 Isomerism
The phenomenon of two or more
compounds having the same number
and kind of atoms
• The various individual compounds
are called isomers.
– e.g. There are two isomers of C4H10.

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 Two isomers for the molecular formula C4H10:
H
H H H H H H
H C H
H C C C C H
H C C C H
H H H H

butane or n-butane H H H
bp = -0.5 C isobutane
mp = -138.3 C bp = -11.7 C
mp = -159.5 C
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 Divisions of Isomers
• Constitutional isomers
– have the same atoms (molecular formula)
but the bonds that connect them are
different.
• Stereoisomers, or spatial isomers
– share the same atoms and bonds but are
arranged differently in space.
• These molecules are defined as chiral.
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 Types of Isomerism

• Structural isomerism
– the difference between isomers is due to
different structural arrangements of the atoms
that form the molecules.
– e.g. butane and isobutane
• Stereoisomerism
– the isomers have the same structural formula,
but differ in spatial arrangement of atoms
(different orientation in space).
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 Structural/Constitutional
Isomerism
H
H H H H H H
H C H
H C C C C H
H C C C H
H H H H

butane or n-butane H H H
bp = -0.5 C isobutane
mp = -138.3 C bp = -11.7 C
mp = -159.5 C
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 Diastreomers and Enantionmers
• Enantiomers
– Mirror images of each other
• Diastereomers
– Not mirror images of each other

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 Geometric Isomers
• Compounds which differ from each other in
the arrangement of groups with respect to a
double bond, ring, or other rigid structure.
• Compounds containing a carbon-carbon
double bond (pi bond) have restricted
rotation about that double bond.
• This restricted rotation in a molecule gives
rise to a type of isomerism known as
geometric isomerism.
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 Geometric Isomers
• Isomers that differ from each other
only in the geometry of their molecules
and not in the order of their atoms are
known as geometric isomers.
• They are also called cis-trans isomers.
• Not mirror images of each other.

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• Types of Isomers:
1. Cis-trans or geometric isomers
2. Optical isomers
– Have the ability to rotate plane-polarized light.

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Geometric Isomerism in Alkenes
• Compounds containing a carbon-carbon
double bond (pi bond) have restricted
rotation about that double bond.
• This restricted rotation in a molecule gives
rise to a type of isomerism known as
geometric isomerism.
• Isomers that differ from each other only in
the geometry of their molecules and not
in the order of their atoms are known as
geometric isomers.
– They are also called cis-trans isomers.
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 1. Cis and Trans or
Geometric Isomers

The same compound

Not Geometric Isomer Cis-Trans isomers
Geometric Isomer

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 Geometric Isomers in Alkenes
Cl Cl H Cl

C C C C

H H Cl H

cis-1,2-dichloroethene trans-1,2-dichloroethene
(bp = 60.1 C) (bp = 48.4 C)
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An alkene shows cis-trans isomerism when
each carbon atom of the double bond has two
different kinds of groups attached to it.

a a a b

C C C C

b b b a

cis isomer trans isomer

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 C3H5Br
• 1-bromo propene
• 2-bromo propene
 C3H4Br2
• 1,1-dibromo propene
• 1,2-dibromo propene
• 1,3-dibromo propene
 2. Optical Isomers
– Have the ability to rotate plane-polarized
light.

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• Plane-polarized light
• is light that is vibrating only in one plane.
– Ordinary (unpolarized) light consists of
electromagnetic waves vibrating in all
directions (planes) perpendicular to the
direction in which it is traveling.
– When ordinary light passes through a
polarizer, it emerges vibrating in only one
plane and is called plane-polarized light.

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Figure 26.1 (a) Diagram of ordinary light vibrating in
all possible directions (planes), and (b) diagram of
plane-polarized light vibrating in a single plane. The
beam of light is coming toward the viewer.
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Figure 26.2 Two
Polaroid filters (top)
with axes parallel and
(bottom) at right angles.
In (a), light passes
through both filters and
emerges polarized. In
(b) the polarized light
that emerges from one
filter is blocked and
does not pass through
the second filter, which
is at right angles to the
first. With no light
emerging, the filters27
appear black.
Figure 26.3 Schematic
diagram of a polarimeter.

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 Specific Rotation [α]
• - is the number of degrees that polarized
light would be rotated by passing through 1
decimeter of a solution of the substance at
a concentration of 1 g/mL.

[α] = Observed rotation in degrees

(length of sample tube in dm)(sample concentration g/mL)

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Optical Activity

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 Optical Activity
• Many naturally occurring substances are
able to rotate the plane of polarized light.
– optically active
• When plane-polarized light passes through
an optically active substance, the plane of
polarized light is rotated.
– right (clockwise) dextrorotatory
– left (counterclockwise) levorotatory
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 Optical Activity
• Louis Pasteur(1822-1895)
– Observed that sodium ammonium
tartrate, a salt of tartaric acid, exists as a
mixture of two kind of crystals.
– Difference in optical activity due to
difference in molecular symmetry.
• J. H van’t Hoff(1852-1911)
– First Nobel prize in chemistry - 1901
• J. A Le Bel(1847-1930)
– They concluded that the presence of at
least one asymmetric carbon atom in a
molecule of an optically active substance
is the key factor for optical activity
 Asymmetry
• The tetrahedral arrangement of single
bonds around a carbon atom makes
asymmetry (lack of symmetry) possible in
organic molecules.
• When four different atoms or functional
groups are bonded to a carbon atom, the
molecule formed is asymmetric, and the
carbon atom is called an asymmetric
carbon atom.
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Figure 19.1 Tetrahedral structure of carbon: (a) a regular
tetrahedron; (b) a carbon atom with tetrahedral bonds; (c) a
carbon atom within a regular tetrahedron; (d) a methane
molecule, CH4
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Figure 26.4 Three-dimensional representation of an
asymmetric carbon atom with four different groups
bonded to it. The carbon atom is a sphere. Bonds to A
and B project from the sphere toward the observer.
Bonds to C and D project from the sphere away from
the observer.
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 Definition of Terms
• Symmetry - sense of balance
• Mirror Image – reflection
• Plane - flat surface
• Plane of Symmetry – imaginary flat
surface that cut the object into two
equal parts

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 Definition of Terms
• Superimposable - put one object on
top of the other; all points will match
• Non-superimposable - put one object
on top of the other; not all points will
match
• Chiral Center - with four different
groups attached
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 Chiral
• - molecule that is not superimposable on
its mirror image.
– e.g. your left and right hands
• An asymmetric carbon atom is also
called a chiral carbon atom or chiral
center.
• A molecule cannot be chiral if it has a
plane of symmetry.
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 Definition of Terms
Enantiomers
- Chiral molecules that are non-
superimposable mirror images of each
other.

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 Definition of Terms
• Plane-polarized light
– is light that is vibrating only in one plane.

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 Projection Formulas
• - representations of molecules with chiral
carbon on paper.

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Figure 26.7 Methods of representing three-
dimensional formulas of a compound that contains one
chiral carbon atom. All three structures represent the
same molecule (lactic acid). Formulas II and III are
called projection formulas. 43
Figure 26.4 Three-dimensional representation of an
asymmetric carbon atom with four different groups
bonded to it. The carbon atom is a sphere. Bonds to A
and B project from the sphere toward the observer.
Bonds to C and D project from the sphere away from
the observer.
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Enantiomers
- Chiral molecules that are non-
superimposable mirror images of each
other.

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Figure 26.8 Mirror images of lactic acid. Each isomer is the mirror
reflection of the other. (-)-Lactic acid rotates plane-polarized light to the
left, and (+)-lactic acid rotates plane-polarized light to the right. They
are enantiomers of one another.- Chiral molecules that are non- 46
superimposable mirror images of each other.
 D and L Enantiomers
• The position of the OH group on the
chiral carbon farthest from the
carbonyl group determines whether the
compound will be of D or L type.

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D and L Glucose
(Enantiomers)

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 D and L Glyceraldehyde
(Enantiomer)

CHO CHO

H C OH HO C H

CH2OH CH2OH
D-glyceraldehyde L-glyceraldehyde
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 Enantiomers

• Same chemical properties

• Same physical properties (except for
optical rotation)
• They rotate plane-polarized light the same
number of degrees, but in opposite
directions.

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 Enantiomers
• Differ in their Biochemical Properties.
– (+)-Glucose (“blood sugar”) is used for
metabolic energy
– (-)-glucose is not.
– (+)-Lactic acid is produced by reactions
occurring in muscle tissue
– (-)-lactic acid is produced by the lactic
acid bacteria in the souring of
milk.(enzyme catalyzed)
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 Enantiomers
• Differ in their Biochemical Properties.

• Ibuprofen(Advil, Motrin, Nuprin)

– Only effective in one of its isomeric form
– Inactive isomer slows the ability of the drug to
reach therapeutic levels.
– Only the active drug can fit into the protein
pocket in the correct way and relieve
inflammation, headache, etc.

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 Enantiomers
• Differ in their Biochemical Properties.

• Thalidomide
– Active enantiomer effective in suppressing
some immune responses.
– Inactive enantiomer of thalidomide causes birth
defects.

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Key Factors of Enantiomers and
Optical Isomerism
1. A carbon atom that has four different
groups bonded to it is called an
asymmetric or chiral carbon atom.
2. A compound with one chiral carbon atom
can exist in two isomeric forms called
enantiomers.
3. Enantiomers are nonsuperimposable
mirror-image isomers.

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 Key Factors of Enantiomers and
Optical Isomerism
4. Enantiomers are optically active; that is, they
rotate plane-polarized light.
5. One isomer of an enantiomeric pair rotates
polarized light to the left (counterclockwise).
The other isomer rotates polarized light to the
right (clockwise). The degree of rotation is the
same but in opposite directions.
6. Rotation of polarized light to the right is
indicated by a (+) and to the left by a (-).
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Racemic Mixtures

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 Racemic Mixtures
• - mixture containing equal amounts of a
pair of enantiomers
• such a mixture is optically inactive and
shows no rotation of polarized light when
tested in a polarimeter.
– Each enantiomer rotates the plane of
polarized light by the same amount, but in
opposite directions. Thus, the rotation by each
isomer is canceled.
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Figure 26.9 Some examples of common chiral drugs. Many
pharmaceuticals are synthesized as racemic mixtures.
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 Importance of Isomerism
• For Enzyme specificity

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Diastereomers and
Meso Compounds

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 Diastereomers
• - exist when there are two or more chiral
carbon atoms in a molecule
• Stereoisomers that are not enantiomers (not
mirror images of each other)
CH 3 CH 3

H Br H Br

H Cl Cl H

CH 3 CH 3

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diastereomers
 Meso Compounds
• - stereoisomers that contain chiral carbon
atoms and are superimposable on their own
mirror images.
• - optically inactive.
COOH

H OH
plane of symmetry
H OH

COOH 63
meso-tartaric acid
 Differences Between Enantiomer
Diastereomer and Meso Compound
• Enantiomers
– Mirror images
– Not superimposable
– Optically active
• Diastereomers
– No mirror image
– Not superimposable
• Meso Compound
– Mirror image
– Superimposable on their own mirror images
– Optically inactive

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Enantiomers and Diastreomers

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 Conformer and Rotamer
• Conformer
– any of a set of stereoisomers
characterised by a conformation that
corresponds to a distinct potential energy
minimum
• Rotamer
– any of a set of conformers that arise from
restricted rotation around a single bond.
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 Summary
• Isomerism
• Divisions of Isomers (Constitutional and
Stereoisomer)
• Types of Stereoisomers (Enantiomers and
Diastereomers)
• Types of Geometric Isomers (Cis and
Trans)
• Optical Isomers
• Meso Compound and Racemic Mixtures 67
• Racemic mixture
– mixture containing equal amounts of a
pair of enantiomers
• Meso Compound
– stereoisomers that contain chiral carbon
atoms and are superimposable on their
own mirror images (with plane of
symmetry).

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• Isomerism is the phenomenon of two or
more compounds having the same number
and kind of atoms.
• In structural isomerism, the difference
between isomers is due to different
structural arrangements of the atoms that
form the molecules.
– e.g. butane and isobutane
• In stereoisomerism, the isomers have the
same structural formula, but differ in spatial
arrangement of atoms. 69
 Difference Between Enantiomer
Diastereomer and Meso Compund
• Enantiomers
– Mirror images
– Not superimposable
– Optically active
• Diastereomers
– No mirror image
– Not superimposable
• Meso Compound
– Mirror image
– Superimposable on their own mirror images
– Optically inactive

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