CHE2201, Chapter 5

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STEREOISOMERS

Stereochemistry at
Tetrahedral
Centers

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 Isomers

Compounds that have the

same molecular formula but
different structures.

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 Constitutional Isomers

Constitutional isomers differ in the way the atoms are connected.

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CHE2201, Chapter 5
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 Cis–Trans Isomers

Cis–trans isomers result from restricted rotation.

Cyclic structures restrict rotation.

Cis: The substituents are on the same side of the ring.

Trans: The substituents are on opposite sides of the ring. CHE2201, Chapter 5
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 Cis–Trans Isomers
Double bonds restrict rotation.

Cis: The hydrogens are on the same side of the double bond.

Trans: The hydrogens are on opposite sides of the double bond.

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 Cis–Trans Isomers

Cis–trans isomers have different physical properties.

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Some Alkenes Do Not Have
Cis–Trans Isomers

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 Different Conformations

Compounds with different conformations (conformers) cannot be separated.

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 Different Configurations

Compounds with different configurations can be separated.

Cis–trans isomers have different configurations.

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 Stereochemistry
• Some objects are not the
same as their mirror
images (technically, they
have no plane of
symmetry)
– A right-hand glove is
different from a left-
hand glove. The
property is commonly
called “handedness”
• Organic molecules
(including many drugs)
have handedness that
results from substitution
patterns on sp3
hybridized carbon
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 Chiral and Achiral Objects
Chiral objects – not superimposable on their mirror image

Achiral objects – superimposable on their mirror image

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 Chiral Molecules

Chiral molecules have an asymmetric center.

An asymmetric center is an atom that is attached to

four different groups.

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Compounds with an Asymmetric Center

Asymmetric centers are also called chirality centers.

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 Enantiomers

The two isomers are called enantiomers.

Enantiomers are different compounds: they can be separated.

Enantiomers have the same physical and chemical properties.

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 Enantiomers

Enantiomers are nonsuperimposable mirror images.

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Chiral and Achiral Molecules

Chiral compounds have nonsuperimposable mirror images.

Achiral compounds have superimposable mirror images

(they are identical molecules).
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 Asymmetric Center versus
Stereocenter

Asymmetric center: an atom attached to four different groups

Stereocenter: an atom at which the interchange of two groups produces a stereoisomer

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 Examples of Enantiomers
• Molecules that have one carbon with 4 different
substituents have a nonsuperimposable mirror image –
enantiomer
• Which of the following are enantiomers?

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The Reason for Handedness: Chirality

• Molecules that are not superimposable

with their mirror images are chiral (have
handedness)
• A plane of symmetry divides an entire
molecule into two pieces that are exact
mirror images
• A molecule with a plane of symmetry is the
same as its mirror image and is said to be
achiral
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Plane of Symmetry

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 Plane of Symmetry
• The plane has the
same thing on both
sides for the flask
• There is no mirror plane
for a hand

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 Asymmetric (Chirality) Centers in
Chiral Molecules
• Groups are considered “different” if there is any
structural variation (if the groups could not be
superimposed if detached, they are different)
• In cyclic molecules, we compare by following in each
direction in a ring

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 Optical Activity

• Light restricted to pass through a plane is plane-

polarized
• Plane-polarized light that passes through solutions of
achiral compounds retains its original plane of
polarization
• Solutions of chiral compounds rotate plane-polarized
light and the molecules are said to be optically active

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Plane-Polarized Light

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An Achiral Compound is Optically Inactive

An achiral compound does not rotate

the plane of polarization of plane-polarized light.

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A Chiral Compound is Optically Active

A chiral compound rotates

the plane of polarization of plane-polarized light.

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 Measurement of Optical
Rotation
• A polarimeter measures the rotation of plane-polarized
light that has passed through a solution
• The source passes through a polarizer and then is
detected at a second polarizer
• The angle between the entrance and exit planes is the
optical rotation.

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 A Polarimeter

• Rotation is measured in degrees, []

• Clockwise rotation is called dextrorotatory = (+)
• Counterclockwise rotation is levorotatory = (-)

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 Specific Rotation
• To have a basis for comparison, we define
specific rotation, []D for an optically
active compound
• []D = observed rotation/(pathlength x
concentration)
= /(l x C) = degrees/(dm x g/mL)
• Specific rotation is that observed for 1 g/mL
in solution in cell with a 10 cm path using
light from sodium metal vapor (589 nm)
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Specific Rotation and Molecules
• Characteristic property of a compound that is optically
active – the compound must be chiral
• The specific rotation of the enantiomer is equal in
magnitude but opposite in sign

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 Pasteur’s Discovery of
Enantiomers
• Louis Pasteur discovered that sodium ammonium salts of tartaric
acid crystallize into right handed and left handed forms
• The optical rotations of equal concentrations of these forms have
opposite optical rotations
• The solutions contain mirror image isomers, called enantiomers
and they crystallized in mirror image shapes – such an event is rare

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 How to Draw Enantiomers
Perspective formulas

Fischer projections

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 Sequence Rules for Specification of
Configuration
• A general method applies to the configuration at each
chirality center (instead of to the whole molecule)
• The configuration is specified by the relative positions of
all the groups with respect to each other at the chirality
center
• The groups are ranked in an established priority
sequence and compared
• The relationship of the groups in priority order in space
determines the label applied to the configuration,
according to a rule

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 Sequence Rules (IUPAC)
Rule 1:
• Look at the four atoms directly attached to the chirality
center, and rank them according to atomic number.
• With the lowest priority group pointing away, look at
remaining 3 groups in a plane
• Clockwise is designated R (from Latin word for “right”)
• Counterclockwise is designated S (from Latin word for
“left”)

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 Sequence Rules (Continued)
Rule 2:
• If a decision cannot be reached by ranking the first atoms
in the substituents, look at the second, third, or fourth
atoms until difference is found

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 Sequence Rules (Continued)
Rule 3:
• Multiple-bonded atoms are equivalent to the same
number of single-bonded atoms

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Naming Enantiomers

Assign relative priorities to the four groups.

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 Naming Enantiomers
draw an arrow from 1 to 2 to 3

if the lowest priority group is on a hatched wedge, then

clockwise = R
and
counterclockwise = S CHE2201, Chapter 5
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 Naming Enantiomers

If the lowest priority group is not on a hatched wedge,

switch a pair so it is on a hatched wedge.

Then, name the new compound.

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 Naming Enantiomers

if the lowest priority group is on a vertical bond, then

clockwise = R
and
counterclockwise = S
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 Naming Enantiomers

if the lowest priority group is on a horizontal bond, then

counterclockwise = R
and
clockwise = S
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R and S Versus (+) and (–)

Some R enantiomers are (+) and some are (–).

Some S enantiomers are (+) and some are (–).

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If One Enantiomer Is (+),
the Other Is (–)

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Compounds with Two Asymmetric Centers

maximum # of stereoisomers = 2n
(n = # of asymmetric centers)

1 and 2 are enantiomers. 3 and 4 are enantiomers.

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 Diastereomers

1 and 2 are enantiomers. 3 and 4 are enantiomers.

Diastereomers are stereoisomers that are not enantiomers.

1 and 3 are diastereomers. 2 and 3 are diastereomers.

1 and 4 are diastereomers. 2 and 4 are diastereomers.

Diastereomers have different physical and chemical properties.

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Let’s Examine 2-amino-3-
hydroxybutanoic acid

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 Two Asymmetric Centers,
Four Stereoisomers

The cis stereoisomers are a pair of enantiomers.

The trans stereoisomers are a pair of enantiomers.

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Identifying an Asymmetric Center

An asymmetric center is attached to four different groups.

two asymmetric centers, four stereoisomers CHE2201, Chapter 5

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No Asymmetric Centers

There are only two stereoisomers: cis and trans.

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No Asymmetric Centers

There are only two stereoisomers: cis and trans.

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 Meso Compounds
• Tartaric acid has two chirality centers and two diastereomeric
forms
• One form is chiral and the other is achiral, but both have two
chirality centers
• An achiral compound with chirality centers is called a meso
compound – it may have a plane of symmetry
• The two structures on the right in the figure are identical so the
compound (2R, 3S) is achiral

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Two Asymmetric Centers: Three Stereoisomers
(a meso compound and a pair of enantiomers)

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 A Meso Compound Has a
Superimposable Mirror Image

Meso compounds are optically inactive even though they have asymmetric centers.

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A Meso Compound Has a
Plane of Symmetry

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 A Meso Compound

A compound with two asymmetric centers that have the same four groups
bonded to each asymmetric center will have three stereoisomers:

a meso compound and a pair of enantiomers.

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 A Meso Compound

For cyclic compounds with the same substituent bonded to

two asymmetric centers,
cis = a meso compound
and
trans = a pair of enantiomers. CHE2201, Chapter 5
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Naming Stereoisomers

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Naming Stereoisomers

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Naming Stereoisomers

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Racemic Mixtures and The Resolution
of Enantiomers
• A 50:50 mixture of two chiral compounds that are mirror
images does not rotate light – called a racemic mixture
(named for “racemic acid” that was the double salt of (+)
and (-) tartaric acid)
• The pure compounds need to be separated or resolved
from the mixture (called a racemate)
• To separate components of a racemate (reversibly) we
make a derivative of each with a chiral substance that is
free of its enantiomer (resolving agent)
• This gives diastereomers that are separated by their
differing solubility
• The resolving agent is then removed

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Racemic Mixtures (Continued)

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Racemic Mixtures (Continued)

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Physical Properties of Stereoisomers

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Separating Enantiomers

separating by hand

separating by chromatography
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Physiological Properties of Enantiomers

Enantiomers can have very different physiological properties.

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 Oranges and Lemons

found in oranges found in lemons

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 Enantiomeric Excess

Enantiomeric excess tells us

how much of an excess of one enantiomer is in a mixture.

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