Stereosomerism

Optical Isomers: These are isomers have

the same physical and chemical characters
but have different interaction with plane-
polarized light. One isomer would rotate
the plane of plane-polarized light to the
right while the other rotates it to the left.
 Biological Activity

Sedative-hypnotic drugs are central nervous system depressants and vary

widely in their potency. They affect your central nervous system – your brain
and spinal cord – and have a relaxing, calming effect.

“ A teratogen is anything a person is exposed to or ingests during

pregnancy that's known to cause fetal abnormalities. Drugs, medicine,
chemicals, certain infections and toxic substances are examples of
teratogens. Teratogens can also increase the risk for miscarriage, preterm
labor or stillbirth.” 2
 Chirality

• “Handedness”: Right-hand glove does

not fit the left hand.
• An object is chiral if its mirror image is
different from the original object.
3
 Achiral
• Mirror images that can be superposed
are achiral (not chiral).

4
 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.
5
 Chiral Carbon Atom
• Also called asymmetric carbon atom.
• Carbon atom that is bonded to four different groups is
chiral (chirality center, stereocenter or stereogenic
center)
• Its mirror image will be a different compound
(enantiomer).

6
 Stereoisomers
Enantiomers: Compounds that are
nonsuperimposable mirror images. Any molecule
that is chiral must have an enantiomer.

7
 Planes of Symmetry

• A molecule that has a plane of symmetry is

achiral.

8
Chiral or not?
How many chiral centers

10
 (R) and (S) Configuration

• Both enantiomers of alanine receive the same name in

the IUPAC system: 2-aminopropanoic acid.
• Only one enantiomer is biologically active. In alanine
only the enantiomer on the left can be metabolized by
the enzyme.

11
 Medicinal/Bio-Chemistry

• Alanine is a non-essential amino acid

that occurs in high levels in its free state
in plasma. It is produced from pyruvate
by transamination. It is involved in sugar
and acid metabolism, increases
immunity, and provides energy for
muscle tissue, brain, and the central
nervous system

12
 Cahn–Ingold–Prelog Priority System
• A way to distinguish between enantioomers is to use
stereochemical modifiers (R) and (S).
• Enantiomers have different arrangements of the four
groups attached to the asymmetric carbon.
• The two possible arrangements are called
configurations.
• Each asymmetric carbon atom is assigned a letter
(R) or (S) based on its three-dimensional
configuration.
• Cahn–Ingold–Prelog convention is the most widely
accepted system for naming the configurations of
chirality centers.

13
(R) and (S) Configuration Step-1: Assign Priority

• Assign a relative “priority” to each group

bonded to the asymmetric carbon.
Group 1 would have the highest priority,
group 2 second, etc.
• Atoms with higher atomic numbers
receive higher priorities.

I > Br > Cl > S > F > O > N > C > H

14
 Assign Priorities

Atomic number: F > N > C > H

15
 (R) and (S) Configuration: Breaking Ties

In case of ties, use the next atoms along

the chain of each group as tiebreakers.

16
 Assign Priorities

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)

17
Configuration in Cyclic Compounds

18
Medicinal/Bio-Chemistry

19
Configuration: R/S Nomenclature
Multiple chiral centers

21
 Properties of Enantiomers

• Same boiling point, melting point, and density.

– 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 have different smells.
• “ Rotate the plane of polarized light in the same
magnitude, but in opposite directions ” ??!!

22
Polarized Vs Unpolarized Light

23
 Polarimeter
Enantiomers rotate the plane of polarized light in opposite
directions, but same magnitude.

Clockwise: Dextrorotatory (+)

Counterclockwise: Levorotatory (-)
Not related to (R) and (S)
24
 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.
25
 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!

26
 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.

27
Fischer Projections (Continued)

28
 Fischer Rules

• Carbon chain is on the vertical line.

• Highest oxidized carbon is at top.
• Rotation of 180 in plane doesn’t
change molecule.
• Rotation of 90 is NOT allowed.

29
 180°- Rotation

• A rotation of 180° is allowed because it will

not change the configuration.

30
 90°-Rotation

• A 90° rotation will change the orientation of

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

31
 When naming (R) and (S) from
Fischer projections with the
hydrogen on a horizontal bond
(toward you instead of away
from you), just apply the normal
rules backward.

32
 Fischer (R) and (S)

• Lowest priority (usually H) comes forward, so

assignment rules are backward!
• Clockwise 1-2-3 is (S) and counterclockwise
1-2-3 is (R).
• Example:
(S)
CH3
H Cl
Cl H
CH3
(S)

33
 Fisher Projections

Examples:
CHO CHO
H OH HO H
H OH HO H
HO H H OH
CH2OH CH2OH

CHO CHO H OH HO H
H OH HO H HO H H OH
CH2OH CH2OH

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 Examples

What is the relationship between:

A and B:
A and C:
A and D:
B and C:
B and D:
C and D:
© 2013 Pearson Education, Inc. 35
 Racemic Mixture
R,R S,S
CO2H CO 2H

H OH HO H

HO H H OH

CO2H CO 2H
Racemic Mixture (Racemate): 50/50 mixture of enantiomers

(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid

o
m.p. C 168-170 168-170 210-212
[] (degrees) - 12 + 12 0
(g/mL) 1.7598 1.7598 1.7723
 Meso Compound
Internal Plane of Symmetry
Optically Inactive

R,S S,R
CO2H CO2H

H OH HO H
mirror
plane
H OH HO H

CO2H CO2H
o
rotate 180
superimposible
 Meso Compounds

Rotation of C by 180°gives D
C is symmetrical, identical to its mirror image, D
C and D are achiral, but have chiral centers
C and D are Meso Compounds

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 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.

© 2013 Pearson Education, Inc. 39

 Diastereomers: Cis-trans Isomerism on
Double Bonds

• These stereoisomers are not mirror

images of each other, so they are not
enantiomers. They are diastereomers.

40
 Diastereomers: Cis-trans Isomerism on Rings

• Cis-trans isomers are not mirror images, so

these are diastereomers.

41
 Diastereomers

• Molecules with two or more chiral carbons.

• Stereoisomers that are not mirror images.

42
 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.

© 2013 Pearson Education, Inc. 43

 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.

44
 Number of Stereoisomers
Number of stereo isomers = 2n
n = number of stereocenters
1 Chiral center  2 stereoisomers

2 Chiral center  4 stereoisomers

45
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 2,3,4-trichlorohexane
How many stereoisomers?

Cl

* * *
Cl Cl
3 asymmetric centers
2n, n= # asymmetric centers (3)
8 stereoisomers
 n = 3; 2n = 8

CH3 CH3 CH3 CH3

S H Cl Cl H R H Cl Cl H
S H Cl Cl H R H Cl Cl H
RH Cl Cl H S Cl H H Cl
CH2CH3 CH2CH3 CH2CH3 CH2CH3

CH3 CH3 CH3 CH3

H Cl Cl H Cl H H Cl
Cl H H Cl H Cl Cl H
H Cl Cl H H Cl Cl H
CH2CH3 CH2CH3 CH2CH3 CH2CH3
 Number of Stereoisomers

The 2n rule will not apply to compounds that may have a

plane of symmetry. 2,3-dibromobutane has only three
stereoisomers: (±) diastereomer and the meso
diastereomer.
48
 Optical Isomerism: Definitions

• Stereoisomers – compounds with the same

connectivity, different arrangement in
space
• Enantiomers – stereoisomers that are non-
superimposible mirror images; only
properties that differ are direction (+ or -)
of optical rotation
• Diastereomers – stereoisomers that are not
mirror images; different compounds
with different physical properties
 More Definitions

• Asymmetric center – sp3 carbon with 4

different groups attached
• Optical activity – the ability to rotate the
plane of plane –polarized light
• Chiral compound – a compound that is
optically active (achiral compound will
not rotate light)
• Polarimeter – device that measures the
optical rotation of the chiral compound
 Stereochemistry in Chemical Reactions

Stereochemistry is very important in

chemistry as you are normally only
interested in one of the stereoisomers.
There are two possibilities:
1. Chiral products from achiral reagents
2. Chiral products from chiral reagents

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 Stereochemistry in Chemical Reactions

Chiral products from achiral reagents:

This commonly results from addition type
reactions that go through a carbocation
intermediate, equal chance of reacting with
either side of the carbocation. Usually results in
a racemic mixture (50:50) of both enantiomers,
i.e.
HBr

Br Br

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 Stereochemistry in Chemical Reactions

Chiral products from chiral reagents:

Since the chiral reagents react with each other
at different rates this results in the production of
diastereomers in unequal amounts. i.e.

OCH3 OCH3 OCH3

HBr

Br Br

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