Chapter
Outline
Chapter 26
Stereoisomerism
The mirror
image of this
children’s
ballet class is
not
superimposable
on
the class.
Introduction to General, Organic, and Biochemistry, 10e
John Wiley & Sons, Inc
Morris Hein, Scott Pattison, and Susan Arena
Chapter
Outline
Course Outline
26.1 Review of Isomerism
26.2 Plane-Polarized Light
26.3 Optical Activity
26.4 Fischer Projection Formulas
26.5 Enantiomers
26.6 Racemic Mixtures
26.7 Diastereomers and Meso Compounds
Chapter 26 Summary
2
Chapter
Outline
Review of Isomerism
1. Isomers are molecules that have the same chemical
formula but differ in either:
(a) how the atoms are connected or,
(b) how the connected atoms are arranged in space.
2. Isomers that differ only in their connectivity are called
structural isomers while those that differ in the spatial
arrangement of their atoms are called stereoisomers.
3
Chapter
Outline
Review of Isomerism
The difference between structural isomers is due to
different structural arrangements of the atoms that form
the molecules.
Examples of structural isomers are shown below.
4
Chapter
Outline
Review of Isomerism
Compounds that have the same structural formulas but
differ in their spatial arrangement are called
stereoisomers. There are two types of stereoisomers.
• Cis–trans or geometric isomers, which we have already
considered.
• Optical isomers, the subject of this chapter.
One feature of optical isomers is that they have the ability
to rotate the plane of plane-polarized light . . .
5
Chapter
Outline
Plane-Polarized Light
Plane-polarized light is light that is vibrating in only one
plane.
Ordinary (unpolarized) light consists of electromagnetic
waves vibrating in all directions (planes) perpendicular
to the direction in which the light is traveling.
6
Chapter
Outline
Plane-Polarized Light
When ordinary light passes through a polarizer, it emerges
vibrating in only one plane and is called plane-polarized
light.
7
Chapter
Outline
Plane-Polarized Light
The rotation of plane-polarized light is quantitatively
measured with an instrument called a polarimeter.
When the sample tube in the polarimeter contains a
solution of a material that is not optically active the
plane of polarized light has been rotated zero degrees.
When the sample tube in the polarimeter contains a
solution of a material that is optically active the plane
of polarized light has been rotated a specific number of
degrees.
8
Chapter
Outline
Plane-Polarized Light
A schematic diagram of a polarimeter measuring an
optically active sample is shown below.
9
Chapter
Outline
Plane-Polarized Light
The specific rotation [α] of an optically active sample can
be calculated using the following formula using the
observed rotation in degrees measured by the polarimter.
10
Chapter
Outline
Optical Activity
Optical activity is the ability of a substance to rotate
plane-polarized light to the right or left.
A substance that rotates polarized light to the right
(clockwise) is said to be dextrorotatory (designated (+)
in the name).
A substance that rotates polarized light to the left
(counterclockwise) is said to be levorotatory
(designated (−) in the name).
11
Chapter
Outline
Optical Activity
A substance that can rotate plane-polarized light is
optically active.
A necessary condition for optical activity is the property
chirality.
Chirality is a property present in an object that cannot be
superimposed on its mirror image.
Chiral objects or chiral molecules do not have a plane of
symmetry. They are asymmetric.
12
Chapter
Outline
Optical Activity
Your right hand and your left
hand are mirror images of each
other.
Your left hand and right hand are
not superimposable.
Therefore your right hand and
your left hand are chiral objects.
Superimposable means that, when we lay one object upon
13
another, all parts of both objects coincide exactly.
Chapter
Outline
Optical Activity
Chirality is typically seen in molecules that have a chiral
or asymmetric carbon atom.
Chiral or asymmetric carbon atoms have four different
atoms or four different group attached to it.
14
Chapter
Outline
Optical Activity
A molecule that is not superimposable on its mirror image
is said to be chiral.
Chiral molecules relate to each other in the same manner
as the right and left hands. They are not
superimposable on their mirror images.
Molecules or objects that are superimposable on each
other are achiral. A molecule is achiral if it has a plane
of symmetry.
15
Chapter
Outline
Your Turn!
Draw the mirror-image isomers for the following
compounds that can exist as stereoisomers.
1) CH3CHOHCH2CH2OH
2) CH3CHBrCH(CH3)2
16
Chapter
Outline
Your Turn!
Draw the mirror-image isomers for the following
compounds that can exist as stereoisomers.
1) CH3CHOHCH2CH2OH
This molecule has a
chiral atom and exists
as two stereoisomers.
The carbon atom in
red is connected to
four different groups.
CH3
H
C
CH3
OH
CH2CH2OH
HO
C
H
CH2CH2OH
17
Chapter
Outline
Your Turn!
Draw the mirror-image isomers for the following
compounds that can exist as enantiomers.
2) CH3CHBrCH(CH3)2
This molecule has a
chiral atom and exists
as two stereoisomers.
The carbon atom in
red is connected to
four different groups.
CH 3
Br
C
CH 3
H
CH(CH 3)2
H
C
Br
CH(CH 3)2
18
Chapter
Outline
Your Turn!
Draw all the structural formulas for the butyl alcohols,
C4H9OH, and indicate which molecules have optical
activity.
19
Chapter
Outline
Your Turn!
Draw all the structural formulas for the butyl alcohols,
C4H9OH, and indicate which molecules have optical
activity.
H
H
H
OH
H
H
OH
There are the
four
structural
isomers.
H
H
C
C
C
C
H
H
H
H
H
OH H
C
C
H
H
C
H
H
H
H
C
H
H
C
H
H
C
H
H
H
H
C
C
H
H
H
OH H
C
C
C
C
H
H
H
20
H
H
Chapter
Outline
Your Turn!
Draw all the structural formulas for the butyl alcohols,
C4H9OH, and indicate which molecules have optical
activity.
H
H
H
OH
H
H
OH
Only one of these
has a chiral atom
and is optically
active. This
atom is
connected to four
different groups.
H
H
C
C
C
C
H
H
H
H
H
OH H
C
C
H
H
C
H
H
H
H
C
H
H
C
H
H
C
H
H
H
H
C
C
H
H
H
OH H
C
C
C
C
H
H
H
H
21
Optically active
H
Chapter
Outline
Fischer Projection Formulas
A Fischer projection is a two-dimensional structural
formula used to represent a three-dimensional structure
on paper.
Figure I is a three-dimensional representation of lactic
acid. Figures II and III are two Fischer projections of
the molecule.
22
Chapter
Outline
Fischer Projection Formulas
In the Fischer Projections II and III:
• The horizontal bonds represent the bonds that project in
front of the paper or toward the viewer.
• The vertical bonds represent the bonds that project
behind the paper or away from the viewer.
23
Chapter
Outline
Fischer Projection Formulas
It is important to be careful when comparing projection
formulas. Two rules apply:
(1) Projection formulas must not be turned 90°.
Projection formulas must not be lifted or flipped out
of the plane of the paper.
(2) Projection formulas may be turned 180° in the plane
of the paper without changing the spatial arrangement
of the molecule.
24
Chapter
Outline
Fischer Projection Formulas
Formulas I, II, III, IV, and V represent the same
molecule. Formula IV was obtained by turning
formula III 180°. Formula V is formula IV drawn in a
three-dimensional representation.
25
Chapter
Outline
Fischer Projection Formulas
If formula III is turned 90°, the other stereoisomer of lactic
acid is represented, as shown in formulas VI and VII.
26
Chapter
Outline
Your Turn!
Are molecules A and B the same molecule?
27
Chapter
Outline
Your Turn!
To answer this question you would perform an in-plane
180 rotation and then determine if the rotated molecule
is superimposable on the other molecule.
28
Chapter
Outline
Your Turn!
A and B are not the same molecules because they are
nonsuperimposable mirror images.
29
Chapter
Outline
Your Turn!
Redraw this Fischer Projection as a three-dimensional
formula.
CH3
H
COOH
CH2CH3
30
Chapter
Outline
Your Turn!
Redraw this Fischer Projection as a three-dimensional
formula.
Horizontal lines project toward the viewer, vertical lines
project away from the viewer, and the circle represents
the chiral carbon atom.
CH 3
CH 3
H
COOH
CH 2CH 3
H
COOH
CH 2CH 3
31
Chapter
Outline
Enantiomers
Enantiomers are optically active, non-superimposable
mirror image molecules that have the property of
chirality.
A molecule that has a nonsuperimposable mirror image is
chiral.
32
Chapter
Outline
Enantiomers
Most chiral molecules consist of enantiomer pairs where:
• (+) is assigned to the enantiomer that rotates polarized
light to the right like (+)-lactic acid.
• (−) is assigned to the enantiomer that rotates polarized
light to the left like (−)-lactic acid.
33
Chapter
Outline
Figure 26.8 These molecules are enantiomers. They are nonsuperimposable mirror images of each other. (−)-Lactic acid rotates
plane-polarized light to the left while (+)-lactic acid rotates planepolarized light to the right.
34
Chapter
Outline
Enantiomers
The Fisher Projections of (−)-lactic acid and (+)-lactic
acid are shown on the right.
35
Chapter
Outline
Your Turn!
Draw mirror-image isomers for any of the compounds
than can exist as enantiomers.
a) CH3CH2CH2CHBrCH2CH2CH3
b) CH2BrCH2CHBrCH2CH3
c) CH3CH2CBr2CH2CH2CH3
36
Chapter
Outline
Your Turn!
Draw mirror-image isomers for any of the compounds
than can exist as enantiomers.
First determine if the molecules have chiral carbon atoms
and can exist as enantiomers.
a) CH3CH2CH2CHBrCH2CH2CH3 No chiral atoms
b) CH2BrCH2CHBrCH2CH3 One chiral atom.
c) CH3CH2CBr2CH2CH2CH3 No chiral atoms
37
Chapter
Outline
Your Turn!
Draw mirror-image isomers for any of the compounds
than can exist as enantiomers.
Draw the mirrror-images of molecule b). These
molecules are enantiomers.
b) CH2BrCH2CHBrCH2CH3
H
BrH2CH 2C
H
CH 2CH 3
Br
H3CH 2C
CH 2CH 2Br
Br
38
Chapter
Outline
Enantiomers
Enantiomers ordinarily have the same chemical
properties, and other than optical rotation, they also
have the same physical properties.
Enantiomers rotate plane-polarized light the same number
of degrees, but in opposite directions.
Enantiomers usually differ in their biochemical
properties. In fact, most living cells are able to use only
one enantiomer of an enantiomeric pair.
39
Chapter
Outline
Enantiomers
The key factors of enantiomers and optical isomerism can
be summarized as follows.
1. A carbon atom that has four different groups bonded to
it is called an asymmetric or a chiral carbon atom.
2. A compound with one chiral carbon atom can exist in
two stereoisomeric forms called enantiomers.
3. Enantiomers are nonsuperimposable mirror-image
isomers.
40
Chapter
Outline
Enantiomers
4. Enantiomers are optically active. They rotate planepolarized 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
(+) placed in front of the name of the compound, and
rotation to the left is indicated by a (−) in the name.
41
Chapter
Outline
Racemic Mixtures
A mixture containing equal amounts of a pair of
enantiomers is known as a racemic mixture.
These mixtures are optically inactive. The mixtures have
no observed rotation in a polarimeter because each
enantiomer rotates the plane of polarized light an equal
amount but in opposite directions so that each rotation
cancels out.
42
Chapter
Outline
Racemic Mixtures
The (±) symbol is often used to designate racemic
mixtures.
For example, a racemic mixture of lactic acid is written as
(±)-lactic acid because this mixture contains equal
molar amounts of (+)-lactic acid and (−)-lactic acid.
43
Chapter
Outline
Racemic Mixtures
Racemic mixtures are usually obtained in laboratory
syntheses of compounds in which a chiral carbon atom
is formed.
For example the catalytic reduction of pyruvic acid (an
achiral compound) to lactic acid produces a racemic
mixture containing equal amounts of (+)- and (−)-lactic
acid:
44
Chapter
Outline
Racemic Mixtures
As a general rule, only one of the isomers is produced in
the biological synthesis of optically active
compounds.
For example, only (+)-lactic acid is produced by
reactions occurring in muscle tissue, and only (−)lactic acid is produced by lactic acid bacteria in the
souring of milk.
45
Chapter
Outline
Racemic Mixtures
Many pharmaceuticals are synthesized as racemic
mixtures since organic syntheses are often not
stereospecific. Typically, only one half of these
racemic mixtures is medically active.
Examples of this are shown Figure 26.9 on the next
slide . . .
46
Chapter
Outline
Racemic Mixtures
Figure 26.9 Some examples of common chiral drugs.
47
Chapter
Outline
Diastereomers and Meso Compounds
The enantiomers are stereoisomers that differ only in the
spatial arrangement of the atoms and groups within the
molecule.
The number of stereoisomers increases as the number of
chiral carbon atoms increases.
The maximum number of stereoisomers for a given
compound is obtained by the formula 2n, where n is the
number of chiral carbon atoms in the molecules.
48
Chapter
Outline
Diastereomers and Meso Compounds
A substance with two nonidentical chiral carbon atoms,
such as 2-bromo-3-chlorobutane, four stereoisomers
are possible (22 = 4).
Formulas XVIII and XIX and formulas XX and XXI are
enantiomers. All four compounds are optically active.
49
Chapter
Outline
Diastereomers and Meso Compounds
Enantiomers XVIII and XIX and enantiomers XX and
XXI are not mirror-image isomers of each other.
Stereoisomers that are not enantiomers (not mirror
images of each other) are called diastereomers.
50
Chapter
Outline
Diastereomers and Meso Compounds
There are four different pairs of diastereomers of 2bromo-3-chlorobutane: XVIII and XX, XVIII and
XXI, XIX and XX, and XIX and XXI.
51
Chapter
Outline
Diastereomers and Meso Compounds
Look at another example. The 2n formula indicates that
four stereoisomers of tartaric acid are possible.
Formulas XXII and XXIII represent nonsuperimposable
mirror-image isomers and are enantiomers.
52
Chapter
Outline
Diastereomers and Meso Compounds
Formulas XXIV and XXV are also mirror images but they
are superimposable.
Formula XXIV and XXV represent the same compound.
Only three stereoisomers of tartaric acid exist.
53
Chapter
Outline
Diastereomers and Meso Compounds
Compound XXIV is achiral and does not rotate polarized
light. A plane of symmetry can be passed between
carbons 2 and 3 so that the top and bottom halves of the
molecule are mirror images.
54
Chapter
Outline
Diastereomers and Meso Compounds
Stereoisomers that contain chiral carbon atoms and are
superimposable on their own mirror images are called
meso compounds, or meso structures.
All meso compounds are optically inactive.
55
Chapter
Outline
Diastereomers and Meso Compounds
The three stereoisomers of tartaric acid are represented
and designated in this fashion.
56
Chapter
Outline
Diastereomers and Meso Compounds
The (+) and (-) isomers are enantiomers. The meso
compound is a diastereomer of the (+) and (-) isomers.
The physical properties of these three isomers are shown
on the next slide . . .
57
Chapter
Outline
Diastereomers and Meso Compounds
The enantomers have identical properties except for the
specific rotation. The diastereomers differ in other physical
properties.
58
Chapter
Outline
Your Turn!
How many stereoisomers exist for the following
compound?
CH 2CH 3
H
OH
H
OH
CH 3
59
Chapter
Outline
Your Turn!
How many stereoisomers exist for the following
compound?
CH 2CH 3
CH 2CH 3
CH 2CH 3
H
OH
HO
H
HO
H
OH
HO
H
H
CH 3
CH 3
Enantiomers
H
CH 2CH 3
H
OH
OH
HO
CH 3
H
CH 3
Enantiomers
There are four stereoisomers. None of these structures are
meso structures.
60
Chapter
Outline
Your Turn!
How many stereoisomers exist for the following
compound?
CH 2CH 3
H
CH 3
H
CH 3
CH 2CH 3
61
Chapter
Outline
Your Turn!
How many stereoisomers exist for the following
compound?
CH 2CH3
CH 2CH 3
CH 2CH 3
H
CH 3
H3C
H
H
H
CH 3
H3C
H
H3C
CH 2CH 3
Meso structures
CH 2CH 3
CH 2CH 3
CH 3
H
CH 2CH3
H3C
H
H
CH 3
CH 2CH 3
Enantiomers
There are three stereoisomers. The first two structures have
a plane of symmetry and are identical. The last two
62
structures are enantiomers.
Chapter
Outline
Chapter 26 Summary
• Isomerism is the phenomenon of two or more
compounds having the same number and kind of
atoms.
• In stereoisomerism the isomers have the same
structural formula but differ in the spatial arrangement
of atoms. Stereoisomers have the same structural
formula but differ in their spatial arrangement.
63
Chapter
Outline
Chapter 26 Summary
• A polarimeter uses two polarizers to measure the
rotation of plane-polarized light caused by a solution
that contains an optically active compound.
• Compounds that are able to rotate polarized light are
said to be optically active. Optical activity is
commonly associated with asymmetric carbon atoms.
• A compound with an asymmetric carbon atom is not
superimposable on its mirror image.
64
Chapter
Outline
Chapter 26 Summary
• A molecule that is not superimposable on its mirror
image is said to be chiral.
• A molecule with one chiral carbon atom can be in two
optically active isomeric forms.
• Fischer projection formulas depict a three-dimensional
molecule as a flat, two-dimensional drawing.
• Chiral molecules that are mirror images of each other
are stereoisomers and are called enantiomers.
65
Chapter
Outline
Chapter 26 Summary
• A mixture containing equal amounts of a pair of
enantiomers is known as a racemic mixture.
• The maximum number of stereoisomers for a given
chiral compound is equal to 2n, where n equals the
number of chiral carbon atoms in the molecule.
• Stereoisomers that are not mirror images (enantiomers)
are called diastereomers.
66
Chapter
Outline
Chapter 26 Summary
• Stereoisomers that contain chiral carbon atoms and are
superimposable on their mirror images are called meso
compounds or meso structures.
• Meso compounds are not optically active and are achiral
compounds.
67