Organic Chemistry, 7th Edition

L. G. Wade, Jr.

Chapter 5
Stereochemistry

© 2010, Prentice Hall

Division of Isomers

Chapter 5 2
 Thalidomide tragedy

O O O O
NH NH
N O N O

O O

"right handed" "left handed"

Morning sickness drug causes birth defects

Chapter 5 3
 Chirality

• “Handedness”: Right glove doesn’t fit

the left hand.
• Mirror-image object is different from the
original object.
Chapter 5 4
 Achiral

• Objects that can be superposed are

achiral.

Chapter 5 5
 Stereoisomers
Enantiomers: Nonsuperimposable mirror
images, different molecules with different
properties.

Chapter 5 6
 Chiral Carbons
• Carbons with four different groups attached
are chiral.
• It’s mirror image will be a different
compound (enantiomer).

Chapter 5 7
 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.
Chapter 5 8
 Planes of Symmetry

• A molecule that has a plane of symmetry is

achiral.

Chapter 5 9
 (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).
Chapter 5 11
 Cahn–Ingold–Prelog
Rules
• Assign a priority number to each group
attached to the chiral carbon.
• Priority is assigned according to atomic
number. The highest atomic number
assigned is the highest priority #1.
• In case of ties, look at the next atoms along
the chain.
• Double and triple bonds are treated like
bonds to duplicate atoms.

Chapter 5 12
 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)
Chapter 5 13
 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.

Chapter 5 14
 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)

Chapter 5 15
 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.

Chapter 5 16
Treatment of Multiple Bonds

Chapter 5 17
Example (Continued)

3
CH3

1
CH 3CH2CH=CH H4
CH 2CH 2CH2CH 3
2

Counterclockwise
(S)

Chapter 5 18
 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.

Chapter 5 21
 Optical Activity
• Enantiomers rotate the plane of polarized
light in opposite directions, but same
number of degrees.

Chapter 5 22
 Polarimeter

Clockwise Counterclockwise
Dextrorotatory (+) Levorotatory (-)

Not related to (R) and (S)

Chapter 5 23
 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.
Chapter 5 24
 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!

Chapter 5 27
 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

Chapter 5 29
 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

2l = 120% l = 60% d = 40%

Chapter 5 30
Isomers with More than One
Asymmetric Carbon
 Maximum of 2n stereoisomers
Enantiomers

Diastereosomers

Enantiomers
 Diastereomers

• Are stereoisomers that are not

enantiomers
• Require the presence of two or more
chiral centers.
• Have different physical and chemical
properties.
• May be separated by physical and
chemical techniques.
Diastereomers
 Comparing Structures
Are the structures connected the same?

yes no

Are they mirror images? Constitutional Isomers

yes no

Enantiomers
All chiral centers will
Is there a plane of symmetry?
be opposite between them.
yes no

Meso Diastereomers
superimposable
53
Chapter 5
 Meso Compounds

• Meso compounds have a plane of symmetry.

• If one image was rotated 180°, then it could be
superimposed on the other image.
• Meso compounds are achiral even though they have
chiral centers.

Chapter 5 54
Nomenclature
 Separating Enantiomers
 Separating Enantiomers is called resolution
 Carried ouy by reacting with enantiomeric pure compound
Separating Enantiomers