Organic Chemistry, 7th Edition

L. G. Wade, Jr.

Chapter 5
Stereochemistry

Copyright 2010 Pearson Education, Inc.

Chirality

Handedness: Right glove doesnt fit

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

Achiral
Objects that can be superposed are
achiral.

Chapter 5

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

Chapter 5

Chiral Carbons
Carbons with four different groups
attached are chiral.
Its mirror image will be a different
compound (enantiomer).

Chapter 5

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

Planes of Symmetry

A molecule that has a plane of symmetry is

achiral.
Chapter 5

Cis and Trans Cyclic Compounds

Cis-1,2-dichlorocyclohexane is achiral because the molecule has

an internal plane of symmetry. Both structures above can be
superimposed.
Trans-1,2-dichlorocyclohexane does not have a plane of
symmetry so the images are nonsuperimposable and the
molecule will have two enantiomers.
Chapter 5

(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

CahnIngoldPrelog
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

10

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

11

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

12

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

13

Example
3

CH2CH3

OH
rotate

CH2CH3

CH3CH2CH2
4

CH3CH2CH2

H
OH
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

14

Treatment of Multiple Bonds

Chapter 5

15

Example (Continued)
3

CH3
1

H4

CH3CH2CH=CH

CH2CH2CH2CH3
2

Counterclockwise
(S)
Chapter 5

16

Solved Problem 1
Drawtheenantiomersof1,3dibromobutaneandlabelthemas(R)and(S).(Makingamodelis
particularlyhelpfulforthistypeofproblem.)

Solution
Thethirdcarbonatomin1,3dibromobutaneisasymmetric.Thebromineatomreceivesfirstpriority,
the(CH2CH2Br)groupsecondpriority,themethylgroupthird,andthehydrogenfourth.The
followingmirrorimagesaredrawnwiththehydrogenatomback,readytoassign(R)or(S)asshown.

Chapter 5

17

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

18

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

Chapter 5

19

Polarimeter

Clockwise

Counterclockwise

Dextrorotatory (+)

Levorotatory (-)

Not related to (R) and (S)

Chapter 5

20

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

21

Solved Problem 2
Whenoneoftheenantiomersof2butanolisplacedinapolarimeter,theobservedrotationis4.05
counterclockwise.Thesolutionwasmadebydiluting6gof2butanoltoatotalof40mL,andthe
solutionwasplacedintoa200mmpolarimetertubeforthemeasurement.Determinethespecific
rotationforthisenantiomerof2butanol.

Solution
Sinceitislevorotatory,thismustbe()2butanolTheconcentrationis6gper40mL=0.15g/ml,and
thepathlengthis200mm=2dm.Thespecificrotationis

[] 25
=
D

4.05
(0.15)(2)

Chapter 5

=13.5

22

Biological Discrimination

Chapter 5

23

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

24

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

Chapter 5

25

Optical Purity
Optical purity (o.p.) is sometimes called
enantiomeric excess (e.e.).
One enantiomer is present in greater
amounts.
o.p. =

observed rotation
rotation of pure enantiomer

Chapter 5

X 100

26

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.

o.p. =

3.18
15.90

2l = 120%

X 100 = 20%
l = 60%
Chapter 5

d = 40%
27

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.

Chapter 5

28

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.
Chapter 5

29

Nonmobile Conformers

The planar conformation of the biphenyl derivative is too

sterically crowded. The compound has no rotation around
the central CC bond and thus it is conformationally
locked.
The staggered conformations are chiral: They are
nonsuperimposable mirror images.
Chapter 5

30

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.

Chapter 5

31

2,3-Pentadiene Is Chiral

Chapter 5

32

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.

Chapter 5

33

Fischer Projections (Continued)

Chapter 5

34

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

Chapter 5

35

180 Rotation

A rotation of 180 is allowed because it will

not change the configuration.

Chapter 5

36

90 Rotation

A 90 rotation will change the orientation of

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

Chapter 5

37

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
Chapter 5

38

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:
CH3

(S)

Cl

Cl

(S)

CH3
Chapter 5

39

Diastereomers
Molecules with two or more chiral carbons.
Stereoisomers that are not mirror images.

Chapter 5

40

Alkenes
Cis-trans isomers are not mirror images, so
these are diastereomers.

Chapter 5

41

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.
Chapter 5

42

Comparing Structures
Are the structures connected the same?
yes

no

Are they mirror images?

yes
Enantiomers
All chiral centers will
be opposite between them.

Constitutional Isomers

no
Is there a plane of symmetry?
yes
Meso
superimposable

Chapter 5

no
Diastereomers
43

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

44

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: () diastereomer and the meso diastereomer.
Chapter 5

45

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.
Chapter 5

46

Resolution of Enantiomers

React the racemic mixture with a pure chiral

compound, such as tartaric acid, to form
diastereomers, then separate them.
Chapter 5

47

Chromatographic
Resolution of Enantiomers

Chapter 5

48