STEREOISOMERS

ARRANGEMENTS IN 3D-SPACE

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Isomers

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Physiological Properties of Stereoisomers
(Enantiomers)

Enantiomers can have very different physiological properties.

found in oranges found in lemons

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 Chirality

“Handedness”: Right glove doesn’t fit the left

hand.
Mirror-image object is different from the
original object.
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 Achiral
Objects that can be superposed are achiral.

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 Stereoisomers
Enantiomers: Nonsuperimposable mirror
images, different molecules with different
properties.

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 Chiral Molecules

Chiral molecules have an asymmetric center.

An asymmetric center is an atom that is
attached todifferent groups.

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 Chiral Carbons
• Carbons with four different groups attached
are chiral.
• It’s mirror image will be a different compound
(enantiomer).

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 Enantiomers

Enantiomers are nonsuperimposable mirror images.

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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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 Achiral Compounds

Take this mirror image and try to superimpose it on the

one to the left matching all the atoms. Everything will
match.

When the images can be superposed the compound is

achiral.
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 Planes of Symmetry

A molecule that has a plane of symmetry is achiral.

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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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 (R) and (S) Nomenclature

• Different molecules (enantiomers) must have different

names.
• Usually only one enantiomer will be biologically active.
• Configuration around the chiral carbon is specified
with (R) and (S).
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 Cahn–Ingold–Prelog Rules
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”)
 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
 Assign (R) or (S)

• Working in 3-D, rotate the molecule so that the

lowest priority group is in back.
• Draw an arrow from highest to lowest priority group.
• Clockwise = (R), Counterclockwise = (S)
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 Assign Priorities

Atomic number: F > N > C > H

Once priorities have been assigned, the lowest priority

group (#4) should be moved to the back if necessary.

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 Assign Priorities

Counterclockwise
(S)

Draw an arrow from Group 1 to Group 2 to Group 3

and back to Group 1. Ignore Group 4.
Clockwise = (R) and Counterclockwise = (S)

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 Example
3
1 CH2CH3
OH
rotate
C 3 2
C 4
2 CH2CH3 CH3CH2CH2 H
CH3CH2CH2
H OH
4 1

Clockwise
(R)

When rotating to put the lowest priority group in the

back, keep one group in place and rotate the other
three.
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 Example (Continued)

3
CH3

1
CH3CH2CH=CH H4
CH2CH2CH2CH3
2

Counterclockwise
(S)

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 Example
Draw the enantiomers of 1,3-dibromobutane and label them as (R) and
(S). (Making a model is particularly helpful for this type of problem.)

Solution
The third carbon atom in 1,3-dibromobutane is asymmetric. The bromine atom receives first
priority, the (–CH2CH2Br) group second priority, the methyl group third, and the hydrogen
fourth. The following mirror images are drawn with the hydrogen atom back, ready to assign
(R) or (S) as shown.

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 Properties of Enantiomers
• Same boiling point, melting point, and density.
• Same refractive index.
• Rotate the plane of polarized light in the same
magnitude, but in opposite directions.
• Different interaction with other chiral molecules:
– Active site of enzymes is selective for a specific
enantiomer.
– Taste buds and scent receptors are also chiral.
Enantiomers may have different smells.

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 Optical Activity
Enantiomersrotate the plane of polarized light
in opposite directions, but same number of
degrees.

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 Polarimeter

Clockwise Counterclockwise
Dextrorotatory (+) Levorotatory (-)

Not related to (R) and (S)

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 Specific Rotation
Observed rotation depends on the length of
the cell and concentration, as well as the
strength of optical activity, temperature, and
wavelength of light.

[] = (observed)
c l
Where  (observed) is the rotation observed in the polarimeter, c is
concentration in g/mL and l is length of sample cell in decimeters.

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 Example
When one of the enantiomers of 2-butanol is placed in a polarimeter, the observed rotation is
4.05° counterclockwise. The solution was made by diluting 6 g of 2-butanol to a total of 40
mL, and the solution was placed into a 200-mm polarimeter tube for the measurement.
Determine the specific rotation for this enantiomer of 2-butanol.

Solution

Since it is levorotatory, this must be (–)-2-butanol The concentration is 6 g per 40 mL = 0.15

g/mL, and the path length is 200 mm = 2 dm. The specific rotation is

– 4.05°
[] 25
D
= = –13.5°
(0.15)(2)

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Biological Discrimination

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 Racemic Mixtures

• Equal quantities of d- and l- enantiomers.

• Notation: (d,l) or ()
• No optical activity.
• The mixture may have different boiling point (b. p.) and melting
point (m. p.) from the enantiomers!

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 Racemic Products
If optically inactive reagents combine to form
a chiral molecule, a racemic mixture is
formed.

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 Optical Purity

• Optical purity (o.p.) is sometimes called

enantiomeric excess (e.e.).
• One enantiomer is present in greater
amounts.
observed rotation
o.p. = X 100
rotation of pure enantiomer

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 Enantiomeric Excess

Enantiomeric excess tells us

how much of an excess of one enantiomeris in a mixture.

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 Calculate % Composition
The specific rotation of (S)-2-iodobutane is +15.90.
Determine the % composition of a mixture of (R)- and
(S)-2-iodobutane if the specific rotation of the
Mixture is -3.18.
Sign is from the enantiomer in excess: levorotatory.

3.18
o.p. = X 100 = 20%
15.90

l = 60% d = 40%

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 R and S Versus (+) and (–)

Some Renantiomers are (+) and some are (–).

Some Senantiomers are (+) and some are (–).

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

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 Chirality of Conformers
• If equilibrium exists between two chiral
conformers, the molecule is not chiral.
• Judge chirality by looking at the most
symmetrical conformer.
• Cyclohexane can be considered to be planar,
on average.

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 Chirality of Conformational Isomers

The two chair conformations of cis-1,2-dibromocyclohexane are nonsuperimposable,

but the interconversion is fast and the molecules are in equilibrium. Any sample would
be racemic and, as such, optically inactive.

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 Nonmobile Conformers

• The planar conformation of the biphenyl derivative is too

sterically crowded. The compound has no rotation around the
central C—C bond and thus it is conformationally locked.
• The staggered conformations are chiral: They are
nonsuperimposable mirror images.

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 Allenes

• Some allenes are chiral even though they do

not have a chiral carbon.
• Central carbon is sp hybridized.
• To be chiral, the groups at the end carbons
must have different groups.

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2,3-Pentadiene Is Chiral

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 Fischer Projections
• Flat representation of a 3-D molecule.
• A chiral carbon is at the intersection of horizontal
and vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.

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Fischer Projections (Continued)

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 Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon is at top.
• Rotation of 180 in plane doesn’t change
molecule.
• Do not rotate 90!

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 180° Rotation

• A rotation of 180° is allowed because it will not

change the configuration.

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 90° Rotation

• A 90° rotation will change the orientation of the

horizontal and vertical groups.
• Do not rotate a Fischer projection 90°.

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 Fischer Mirror Images
• Fisher projections are easy to draw and make it
easier to find enantiomers and internal mirror
planes when the molecule has 2 or more chiral
centers.
CH3
H Cl
Cl H
CH3

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 Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so
assignment rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3
is (R).
• Example:
(S)
CH3
H Cl
Cl H
CH3
(S)

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Compounds with Two Asymmetric Centers
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. 50

 A Meso Compound Has a
Superimposable Mirror Image

Meso compounds are optically inactive even though they have asymmetric centers.
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Two Asymmetric Centers: Three Stereoisomers
(a meso compound and a pair of enantiomers)

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 Number of Stereoisomers

The 2n rule will not apply to compounds that may have a plane of symmetry. 2,3-
dibromobutane has only 3 stereoisomers: (±) enantiomerand the mesodiastereomer.

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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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 Two Asymmetric Centers,
Four Stereoisomers

The cisstereoisomers are a pair of enantiomers.

The trans stereoisomersare 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 56

 No Asymmetric Centers

There are only two stereoisomers: cis and

trans.

There are only two stereoisomers: cis and

trans
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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. 58
 Two or More Chiral Carbons
• When compounds have two or more chiral
centers they have enantiomers, diastereomers, or
meso isomers.
• Enantiomers have opposite configurations at each
corresponding chiral carbon.
• Diastereomers have some matching, some
opposite configurations.
• Meso compounds have internal mirror planes.
• Maximum number of isomers is 2n, where n = the
number of chiral carbons.

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 Comparing Structures
Are the structures connected the same?

yes no

Are they mirror images? Constitutional Isomers

yes no

Enantiomers Is there a plane of symmetry?

All chiral centers will
be opposite between them.
yes no

Meso Diastereomers
superimposable
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 Properties of Diastereomers
• Diastereomers have different physical properties,
so they can be easily separated.
• Enantiomers differ only in reaction with other
chiral molecules and the direction in which
polarized light is rotated.
• Enantiomers are difficult to separate.
• Convert enantiomers into diastereomers to be
able to separate them.

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 Resolution of Enantiomers

React the racemic mixture with a pure chiral

compound, such as tartaric acid, to form
diastereomers, then separate them.

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 Chromatographic
Resolution of Enantiomers

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Separating Enantiomers

separating by hand

separating by chromatography
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Physical Properties of Stereoisomers

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Nitrogen and Phosphorus Can Be Asymmetric
Centers

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