Ch506/25

Chapter 5
Stereochemistry

© 2013 Pearson Education, Inc.


ISOMERS
rotation about
Compounds with the single bonds
same molecular formula
Conformations
same different
connectivity connectivity rotation
restricted
Stereoisomers Constitutional Conformational
Isomers Isomers
stereocenters
but no chiral centers with chiral centers
Atropisomers
Cis,Trans m ore than
(E,Z) Isomers one chiral center one chiral center
(can be called achiral chiral
diastereomers)
mirror Enantiomers
Meso not mirror
images images
Compounds

Diastereomers Enantiomers
2

Achiral: Objects, molecules, that contain
mirror elements of symmetry
plane

HO OH

© 2013 Pearson Education, Inc. Chapter 5 3

Planes of Symmetry

• A molecule that has a plane of symmetry is
achiral.


Chirality: Handedness”:
An object, molecule that lacks elements
of symmetry.

Right-hand glove does not fit the left
hand, it is chiral, its mirror image is
different from the original


Enantiomers: a type of
stereoisomers
Compounds that are __________________mirror
images.


Stereocenters: chirality centers,
stereogenic atom
• Chiral or asymmetric carbon bonded to ______ different
groups is the most common type of a chirality center
• Its mirror image will be _________compound (enantiomer).

The double-bonded carbon atoms in cis-trans isomers are
the most common types of stereocenters.

Examples of Chirality Centers:
stereocenters


Cis Cyclic Compounds

• Cis-1,2-dichlorocyclohexane is _______
because the molecule _______internal plane
of symmetry. Both structures above are
_______________


Trans Cyclic Compounds

• Trans-1,2-dichlorocyclopentane
_________have a plane of symmetry so the
images are ______________and the
molecules above are _______________

•
• Only one enantiomer of alanine is biologically active
(only the left enantiomer can be metabolized by the
enzyme)
• Need a way to distinguish between them.


( ) and ( ) Absolute configuration; The Cahn–
Ingold–Prelog Convention
• Assign a relative “priority” to each group
bonded to the asymmetric carbon
according to Z
I Br Cl S F O N 13
C C
12
H
2
H
1


In case of ties, use the next atoms along
the chain of each group as tiebreakers.

If the atoms are the same triple bonds takes priority over
double and double over single


• Lowest priority group
goes to the back.
• Draw an arrow from
highest to lowest priority
group.
• Clockwise = (R),
Counterclockwise = (S)


Determine absolute
configuration

CH2 Br
HS H2CH2 C CH(CH3)2
CN
C C
CH2 CH3
IH2CH2 C
Cl C
ClH2 C CF 3 H2 NH2 C
CH2 OH
H


Assign Absolute Configuration
CH3 CH3
O O
OH OH
OH H H OH
C C C C

CH2 CH2
H H
OH OH
CH 3 CH3
CH3 CH3

CH3 CH3

C H H Cl
l C C

CH2 CH2

CH3 CH3

16

Draw the enantiomers of 1,3-dibromobutane and label
them as (R) and (S). (Build the models)


OH

18

Properties of Enantiomers
• Same boiling point, melting point, and density,
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.


Optical Activity: the rotation of the angle of
polarized light Clockwise Counterclockwise
Dextorotatory (+) Levorotatory (-)
Not related to (R) and (S)


Specific Rotation
Observed rotation depends on temperature, wavelength of
light, _________________________________________
Normalize:

[α] = α (observed)
c•l
α(observed) is the rotation observed in the polarimeter

c is concentration in g/mL,

l is length of sample cell in decimeters.


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.


Biological
Discrimination


____________ Mixtures

• Equal quantities of + and – ; Old notation (d,l); new
(±). No optical activity.
• Can be formed from reactions of achiral compounds


Optical Purity (o.p.) sometimes called
enantiomeric excess (e.e.)

observed rotation
o.p. = X 100
rotation of pure enantiomer

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°.


A commercial synthesis of naproxen, a
nonsteroidal anti-inflammatory drug (NSAID),
gives the S enantiomer in 97% ee
Calculate the percentages of the R and S
enantiomers in this mixture.
CH3

COOH
H3 CO
(S)-Naproxen

26

Chiral compounds that do not posses a
chiral carbon
A) Atropisomers

• 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 ____________: They
are non-superimposable mirror images.

B) Allenes: Some allenes are chiral even
though they do not have a chiral carbon
Build the model


Fischer Projections: Flat representation of
a 3-D molecule
A _________________is at the intersection of
horizontal and vertical lines.
_____________ lines are forward, towards you.
___________ lines are behind the plane. Away
from you


Stereoisomers or same
compounds?
CH3 CH2CH3

H H
Cl CH3
CH2CH3 Cl

CH2CH3 H CH2CH3 CH3

Cl CH3 Cl CH3 H Cl Cl H

H CH2CH3 CH3 CH2CH3

30

Stereoisomers = 2n maximum
3-chloro-2-butanol: Identify enantiomers and diasteromers

31

2,3-dihydroxybutandioic (tartaric acid).
The 2n rule will not apply to compounds that
have a plane of symmetry: a meso compound

Assign absolute configuration to each stereocenter

32

Meso Compounds are achiral even though they
have chiral centers because they have
_____________________


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.

The two chair conformations of cis-1,2-dibromocyclohexane
are _____________________, but the interconversion is fast
and the molecules are in equilibrium. Any sample would be
________________ and, as such, ___________________.

Cyclic molecules
• 2-methylcyclopentanol (4)

• 1,3-cyclopentanediol (3, cis is meso)

35

Disubstituted derivatives of cycloehexane
Methylcyclohexanols (2 Methylcyclohexanol = 4)

4-methylcyclohexanol (2)

3-methyl cyclohexanol (4)

36

Disubstituted derivatives of cycloehexane
Cyclohexanediol
cis-1,2 rapid interconversion = meso

1,3-cyclohexanediol (3)

37

•
Physical properties
Enantiomers have identical physical and chemical properties in achiral
environments (except one)
• Diastereomers are different compounds and have different physical and chemical
properties.

COOH COOH COOH

H C OH HO C H H C OH
HO C H H C OH H C OH

COOH COOH COOH
(R,R)-Tartaric acid (S,S)-Tartaric acid Meso tartaric acid
specific rotation +12.7 -12.7 0
melting point (¡ C) 171-174 171-174 146-148
density at 20¡C (g/cm 3 ) 1.7598 1.7598 1.660
solubility in water at 20¡C (g/100 mL) 139 139 125
pK1 (25¡ C) 2.98 2.98 3.23
pK2 (25¡C) 4.34 4.34 4.82

38

Diastereomers: Cis-trans Isomerism on
Double Bonds
• These stereoisomers are not mirror
images of each other, so they are not
___________. They are diastereomers.


Diastereomers: Cis-trans
Isomerism on Rings
• Cis-trans isomers are not mirror images, so
these are diastereomers.


Comparing Structures


Resolution (separation) of
enantiomers
• In 1848, Louis Pasteur
noticed that a salt of
racemic (±)-tartaric acid
crystallizes into mirror-
image crystals.
• Using a microscope and a
pair of tweezers, he
physically separated the
enantiomeric crystals.
• Pasteur had accomplished
the first artificial resolution
of enantiomers.

Chemical Resolution of
Enantiomers

React the _______________with a ______
chiral compound, such as tartaric acid, to
form _________________, then separate
them.

Resolution of (R)- and (S)-2-butanol


Chromatographic
____________of Enantiomers


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