CM2127 – Organic Chemistry

Stereochemistry

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 Objectives of this lecture

• Explain the different types of isomerism.

• Identify molecules with chiral centres.

• Name molecules with chiral centres.

• Rotate molecules with chiral centres.

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 Isomers
Compounds that have the same molecular formula but
different structures.

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 Isomers
• 2 main classes of isomers:

1) Constitutional isomers (or structural isomers)

differ in the way the atoms are connected.

2) Stereoisomers have their atoms connected in

the same sequence but different spatial
orientation.

• Stereochemistry involves the study of the relative

spatial arrangement of atoms that form the
structure of molecules.
https://en.wikipedia.org/wiki/Stereochemistry 4
 Constitutional Isomers
Constitutional isomers (or structural isomers) differ in the
way the atoms are connected (different sequence).

H H H H H H H H CH3

H C C C C C H H C C CH2CH3 H C C CH3

H H H H H H CH3 H CH3

n-pentane isopentane 2,2-dimethylpropane

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 Isomers
• Stereoisomers have their atoms connected in the
same sequence but different spatial orientation.

• 2 main types of stereoisomers

1) Diastereomers are not mirror-images of
each other
o e.g. cis-trans isomers.
2) Enantiomers are non-superimposable
mirror-images of each other.

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 Stereoisomers : cis–trans Isomers
cis–trans isomers result from restricted rotation.
- Cyclic structures restrict rotation.

H H CH3 H

CH3 CH3 H CH3

cis-1,2-dimethylcyclohexane trans-1,2-dimethylcyclohexane

cis: The substituents are on the same side (top or bottom)

of the ring.
trans: The substituents are on opposite sides of the ring.
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 Isomers
• Stereoisomers have their atoms connected in the
same sequence but different spatial orientation.

• 2 main types of stereoisomers

1) Diastereomers are not mirror-images of
each other
o e.g. cis-trans isomers.
2) Enantiomers are non-superimposable
mirror-images of each other.
o Enantiomers are molecules which are
chiral.

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 Chiral and Achiral Objects
• An object is chiral if it is distinguishable from its
mirror image; that is, it cannot be superposed onto it.

Chiral objects

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 Chiral and Achiral Objects
• Conversely, a mirror image of an achiral object, such
as a sphere, cannot be distinguished from the object.

Achiral objects

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 Chiral Molecules
• Chiral molecules have an asymmetric center (*).
• An asymmetric center is an atom that is attached to
four different groups.

Br C Cl

https://en.wikipedia.org/wiki/File:Chiral.svg 11
 Compounds with an Asymmetric Center
CH3CH2CH2CHCH2CH2CH2CH3
|
OH 4-octanol

CH3CHCH2CH3
|
Br 2-bromobutane
CH3
|
CH3CHCH2CHCH2CH3 2,4-dimethylhexane
|
CH3
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 Enantiomers
The 2 stereoisomers of bromochlorofluoromethane

• The two isomers are called enantiomers

• Enantiomers are different compounds: they can be
separated.
• Enantiomers have the same physical and chemical
properties. 13
 Enantiomers

Enantiomers are nonsuperimposable mirror images.

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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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 Enantiomers

• Video (enantiomers)
• https://www.youtube.com/watch?v=UX5lwbnAAcw
• 0:00-3:00

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 How to Draw Enantiomers
Perspective formulas of the enantiomers of
bromochlorofluoromethane.

Bond in plane of page

F Bond going into page F

C C
H Br Cl
H
Cl Br
Bond going out of page
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 Naming Enantiomers
• R,S-system (Cahn-Ingold-Prelog system).
• Assign relative priorities to the four groups.
• Start with the first atom of each group that is directly
attached to the chiral tetrahedral center.  The atoms
with higher atomic number will have highest priority. 
• If two groups have the same first atom, then compare
the second atom from the chiral center. If there are
multiple second atoms, then compare them in order of
atomic number.
F

C
H Br
Cl 18
 Naming Enantiomers
1) Rotate the molecule so that the lowest priority group
(4) is pointing away from your eye.
2) Then trace a path from priority groups 1 to 2 to 3.
• If the direction is clockwise, the enantiomer is R.
• If the direction is anticlockwise, the enantiomer is S.

F F

C C
H Br H Cl
Cl Br
(S)-bromochlorofluoromethane
(R)-bromochlorofluoromethane
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 Naming Enantiomers

Br H
C C
CH3CH2 H Br
CH3 CH3CH2
CH3

(S)-2-bromobutane -2-bromobutane

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 Revision Quiz 3
What is the relationship between the two
compounds shown below?
CH3 H

C C
H Cl
Cl CH3

A. Enantiomers
B. Diastereomers
C. Constitutional isomers
D. Geometric isomers
E. Identical compounds
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 Revision Quiz 7
Which of the following structures (1/2/3) is the same as
(R)-2-chlorobutane?

H Cl
A. 1

B. 2
CH3
C. 3 H Cl H H

D. 1 & 3 H Cl H
Cl
CH3

E. 2 & 3 1 2 3
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 Amines can undergo Amine Inversion
If one of the four groups attached to N is a lone pair, it can
undergo nitrogen inversion where it “turns inside out”.
enantiomers

sp3 nitrogen sp2 nitrogen sp3 nitrogen

http://chemistry.stackexchange.com/questions/50106/can-heteroatoms-with-lone-pairs-be-chiral-centres
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 Summary

• Explain the different types of isomerism.

• Identify molecules with chiral centres.

• Name molecules with chiral centres.

• Rotate molecules with chiral centres.

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CM2127 – Organic Chemistry

Stereochemistry

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 Objectives of this lecture
• Importance of stereochemistry.

• Properties of enantiomers.

• Molecules with more than 1 chiral centre.

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 Importance of stereochemistry
• Enzymes, which are chiral, often distinguish
between the two enantiomers of a chiral substrate.

• Many biologically active molecules are chiral.

• In drugs, for example, often only one of a drug's

enantiomers is responsible for the desired
physiologic effects, while the other enantiomer is
less active, inactive, or sometimes even productive
of adverse effects.

https://en.wikipedia.org/wiki/Enantiomer
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 A lesson from history
• The thalidomide disaster.
• Thalidomide is a pharmaceutical drug, first prepared
in 1957 in Germany, prescribed for treating morning
sickness in pregnant women.
• The drug was discovered to be teratogenic, causing
serious genetic damage to early embryonic growth and
development, leading to limb deformation in babies.

https://en.wikipedia.org/wiki/Stereochemistry
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Physiological Properties of Enantiomers

 levomethamphetamine
Active ingredient in Vick vapor inhaler

Dextromethamphetamine
Central nervous system (CNS) stimulant 29
 Plane-Polarized Light
Normal light: light rays
oscillate in all directions

light rays oscillate

in a single direction

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 Plane-Polarized Light
The plane of polarization
has been rotated

Sample tube containing

a chiral compound

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 Plane-polarized light
• Video (what is plane-polarized light)
• https://www.youtube.com/watch?v=gP751qpm4n4
• 0:00 – 3:00

• How an chiral compound rotates the plane of

polarized light
• https://www.youtube.com/watch?v=L3qNc8lUdMU
• 1.5 min

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 Optical activity
• A chiral compound rotates the plane of polarization of
plane-polarized light. It is said to be optically active.
1) If it rotates the plane clockwise = (+)
2) If it rotates the place counterclockwise = (–)

• An achiral compound does not rotate the plane of

polarization of plane-polarized light. It is optically
inactive.

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 Specific rotation

The specific rotation [a] is a physical property and is

defined as the measured optical rotation α (in degrees) at
a path length l of 1 dm, a concentration c of 1 g/100 mL,
a temperature T (usually 20°C) and a light wavelength λ
(usually sodium D line at 589.3 nm).

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 R and S Versus (+) and (–)

Some R enantiomers are (+) and some are (–).

Some S enantiomers are (+) and some are (–).

CH3 CH3

C C
HO H HO H
COOH COO-Na+
(S)-(+)-lactic acid (S)-(+)-sodium lactate

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

CH2OH CH2OH

C C
H3C H H 3C CH2CH3
CH2CH3 H

(R)-2-methyl-1-butanol (S)-2-methyl-1-butanol
[ ]20
D
C
 5.75 [ ]20
D
C
 5.75

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 Racemic mixtures
• A solution containing equal amounts of both (+) and
(-) enantiomers is called a racemic mixture.

• A racemic mixture is optically inactive.

• If a solution contains a mixture of both enantiomers,

but one of them is in excess, then the solution is
optically active, but the specific rotation will be less
than that of the pure enantiomer.

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 Enantiomeric Excess
Enantiomeric excess tells us how much of an excess
of one enantiomer is in a mixture.

observed specific rotation

enantiomer ic excess   100%
specific rotation of the pure enationmer

Example:
 9.2
enantiomeric excess   100%  40%
 23.1
In this mixture, 40% consist of the (+) enantiomer
and 60% consist of the racemic form.
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 Revision Quiz 2
A sample of the disulfide L-cystine has an observed
specific rotation of –14°. Pure L-cystine has a specific
rotation of –70°. What percent of each enantiomer is
present in the sample?

A. 14 (–) & 56 (+)

B. 20 (–) & 80 (+)
C. 60 (–) & 40 (+)
D. 80 (–) & 20 (+)
E. 84 (–) & 16 (+)

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Compounds with Two Asymmetric Centers
* *
CH3CHCHCH3
| |
Cl OH
3-chloro-2-butanol

• 3-chloro-2-butanol has 2 asymmetric centres.

• It has a total of 4 stereoisomers.

• In general, maximum # of stereoisomers = 2n

where n = # of asymmetric centers

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 Fisher projection
Fisher projections of 3-chloro-2-butanol
• All horizontal bonds point towards the viewer.
• All vertical bonds point away from the viewer.

CH3 CH3

H OH H OH

H Cl H Cl

CH3 CH3

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Compounds with Two Asymmetric Centers

CH3 CH3 CH3 CH3

H OH HO H H OH HO H

H Cl Cl H Cl H H Cl

CH3 CH3 CH3 CH3

1 2 3 4
1 and 2 are enantiomers. 3 and 4 are enantiomers.
• The following pairs are diastereomers:
1 and 3; 2 and 3; 1 and 4; 2 and 4.
• Diastereomers are stereoisomers that are not mirror images of
each other.
• Diastereomers have different physical and chemical properties.42
Compounds with Two Asymmetric Centers

1 2
1 and 2 are enantiomers. 43
Compounds with Two Asymmetric Centers

3 4
3 and 4 are enantiomers. 44
 Diastereomers

• Video (diastereomers)
• https://www.youtube.com/watch?v=UX5lwbnAAcw
• 3:00-7:00

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Compounds with Two Asymmetric Centers

Br CH3 H3C Br Br CH3 H3C Br

cis-1-bromo-2- trans-1-bromo-2-
methylcyclopentane methylcyclopentane

The cis stereoisomers are a pair of enantiomers.

The trans stereoisomers are a pair of enantiomers.
An asymmetric center is attached to four different groups.
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Compounds with no Asymmetric Centers

cis-1-bromo-4- Br CH3
methylcyclohexane

trans-1-bromo-4-
Br CH3
methylcyclohexane

There are only two stereoisomers: cis and trans.

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Compounds with Two Asymmetric Centers

Some molecules with 2 asymmetric centres have only 3

stereoisomers instead of the maximum 4.

* *
CH3CHCHCH3
| |
Br Br
2,3-dibromobutane

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Compounds with Two Asymmetric Centers
CH3 CH3 CH3 CH3

H OH HO H H OH HO H

HO H H OH H OH HO H

CH3 CH3 CH3 CH3

1 2 3 4

1 and 2 are enantiomers. 3 and 4 are the same.

• The following pairs are diastereomers: 1 and 3; 2 and 3.

• 3 is a meso compound.
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Compounds with Two Asymmetric Centers

1 2
1 and 2 are enantiomers. 50
Compounds with Two Asymmetric Centers

3 4
3 and 4 are the same (meso). 51
 Meso compounds

• Video (meso)
• https://www.youtube.com/watch?v=UX5lwbnAAcw
• 7:00 – 12:00 (meso + summary of everything)

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 Meso compounds
• A meso compound has a superimposable mirror image.
• Meso compounds are optically inactive even though
they have asymmetric centers.
• Test for meso compound:
1) Construct (or draw) a model or
2) A meso compound has a plane of symmetry.
CH3 CH3 CH3

H OH HO H HO H
HO H H OH HO H
CH3 CH3 CH3
1 2 3 53
 A Meso Compound
Generally, 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.

https://en.wikipedia.org/wiki/Meso_compound 54
 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.

https://en.wikipedia.org/wiki/Meso_compound 55
 Naming Stereoisomers
• Use R,S-system as before.
• Each asymmetric C must be denoted R or S.

Br
H
H
HO

(2S, 3R)-3-bromo-2-butanol

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 Physical Properties of Stereoisomers

Melting Specific Solubility

point rotation g/100 g water at 15°C
(2R,3R)-tartaric
171°C +11.98° 139
acid
(2S,3S)-tartaric
171°C −11.98° 139
acid
Meso
146° 0 125
compound
Racemic
206 0 139
mixture
By JaGa - self-made using BKChem and Inkscape, CC BY-SA 3.0,
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 Summary
• Importance of stereochemistry.

• Properties of enantiomers.

• Molecules with more than 1 chiral centre.

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