Geometric isomerism of alkenes, cyclic compounds: cis-trans and (E)-(Z) system of nomenclature b) Conformational isomers: Open chain and cyclic system c) Chirality of molecules: Enantiomers, diastereomers, racemic modification, Meso compound, R & S configuration, sequence rule, Optical rotation d) Asymmetric synthesis: Preparation of enantiomers by asymmetric synthesis & optical resolution method e) Stereo selective and stereo specific reaction f) Pharmaceutical importance of studding stereochemistry

2. Let’s consider some molecules……
First
H
pair
Br
same molecular formula (CH2BrCl)
same atom connectivity
superposableH
Br
A
H
Cl
Cl H
B
Second
H
pair
same molecular formula
same atom connectivity
nonsuperposable
(CHFBrCl)F
F
Br
H
Br
Cl Cl
C D
3
stereoisomers
(two different compounds)
identical (same compound)

3. Thus, we can define………
Stereoisomers: isomersthat have
sameformula and connectivitybut differ in
the position of the atoms in space
Stereochemistry: chemistry that
studies the properties of stereoisomers
4

4. Stereochemistry is a Greek word in which ‘stereos’ means solid.
Stereochemistry deals with the spatial arrangements of atoms and groups in a
molecule.
Stereochemistry refers to the 3-dimensional properties and reactions of
molecules.
It has its own language and terms that need to be learned in order to fully
communicate and understand the concepts.
Stereochemistry includes methods for determining and describing the
relationships of atoms within molecules; The effect these relationships on the
physical or biological properties of the molecules. The manner in which these
relationships influence the reactivity of the molecules (dynamic
stereochemistry).

5. Isomers
Compounds with the
same molecular formula
Conformational
Is ome rs
rotation about
single bonds
with ch iral centers
Stereoisomers
Meso
Compounds
Enantiomers
Constitutional
Is ome rs
Cis,Trans
(E,Z) Is ome rs
(can be called
diastereomers)
Conformations
rotation
re stricted
different
connectivity
Diaste reomers
stereocenters
but no ch iral centers
Enantiomers
one chiral center
m ore than
one chiral center
chiralachiral
not mirror
images
mirror
images
Atropisomers
same
connectivity

6. Isomers types
1. Constitutional : isomers differ in the order in which the atoms are connected so
they can contain different functional groups and / or bonding patterns (e.g. branchi
ng) example: 1-propanol, 2-propanol and ethyl methyl ether (C3H8O)
2. Conformational isomers
stereoisomers that are produced by rotation about σ bond( single bond) , and are often
rapidly interconverted at room temperature
Example :

7. • Conformational isomers are interconvertible by rotations about single
bonds, and the conformation of a molecule concerns features related to
rotations about single bonds
• A related term is atropisomers, which are stereoisomers that can be
interconverted by rotation about single bonds but for which the barrier
to rotation is large enough that the stereoisomers can be separated and
do not interconvert readily at room temperature.
• Atropisomerism is that kind of isomerism, where the conformers
(called atropisomers) can be isolated as separate chemical species
and which arise from restricted rotation about a single bond.

8. OPTICAL ISOMERISM
Occurrence another form of stereoisomerism
occurs when compounds have non-superimposable mirror images
Isomers the two different forms are known as optical isomers or enantiomers
they occur when molecules have a chiral centre
a chiral centre contains an asymmetric carbon atom
an asymmetric carbon has four different atoms (or groups)
arranged tetrahedrally around it.

9. OPTICAL ISOMERISM
Occurrence another form of stereoisomerism
occurs when compounds have non-superimposable mirror images
Isomers the two different forms are known as optical isomers or enantiomers
they occur when molecules have a chiral centre
a chiral centre contains an asymmetric carbon atom
an asymmetric carbon has four different atoms (or groups)
arranged tetrahedrally around it.
There are four different colours
arranged tetrahedrally about th
e carbon atom
2-chlorobutane exhibits optical isomerism
because the second carbon atom has four
different atoms/groups attached
CHIRAL CENTRES

10. A chiral object is that which has non superimposable mirror image.
Chiral Center
An atom with four different groups attached
to it, is called chiral atom and also called
chiral center.
Chirality

11. Any object that has a plane or point of symmetry is achiral
(not chiral). e.g. 2-chloropropane
An atom with four different groups are not attached to it, is
called achiral atom.
Achiral

12. Enantiomers are stereoisomers that are non-superimposable on
their mirror images.
Enantiomers

13. Enantiomers
Enantiomers are that isomers, which are mirror image of each other, i.e.
they are not super imposable.
Enantiomers have identical physical and chemical properties, except in two
important respects-
1. They rotate the plane of polarized light in opposite direction, though in
equal amounts. The isomers which rotates the plane to the left (counter
clockwise) is called the Levo isomer and designated as (-), while the one
which rotates the plane to the right (clockwise) is called dextro isomer and
is designated as (+).
2. They react at different rates with other optically active compounds. It is
for this reason that many compounds are biologically active while their
enantiomers are not.

14. Meso compounds
Meso compounds
A meso compound is one whose molecules are super-imposable
on their mirror images even though they contain chiral centres.

15. Diastereomers are stereoisomers that are not mirror images of
each other – they are stereoisomers that are not enantiomers.
Diastereomers
Diastereoisomers rotate the plane of polarization by different amount and
are not identical in configuration and are not mirror images of each other.
Diastereoisomers differ in physical properties such as melting point,
density, solubility, refractive index etc.

16. Enanatiomers
“Optical isomer”
Same carbon
Same connection
Are mirror image
Nonsuperimposable
All configurations
are opposite
Diastereomers
Same carbon
Same connection
Are Not mirror image
Nonsuperimposable
Not All configurations
are opposite

17. Chiral
 Enantiomers are chiral:
 Chiral:
Not superimposable on its mirror image
 Many natural and man-made objects are chiral:
 hands
 scissors
 screws (left-handed vs. right-handed threads)
Right hand threads
slope up to the right.

18. Chiral
 Some molecules are chiral:
Asymmetric
(chiral) carbon

19. Asymmetric Carbons
 The most common feature that leads to chirality in
organic compounds is the presence of an
asymmetric (or chiral) carbon atom.
 A carbon atom that is bonded to four different
groups
 In general:
 no asymmetric C usually achiral
 1 asymmetric C always chiral
 > 2 asymmetric C may or may not be
chiral

20. Asymmetric Carbons
Example: Identify all asymmetric carbons
present in the following compounds.
C C C C
OH
H
H
H
H
H
H H
H
H H3C
CH3
CH2CH3
H H H
BrBr
Br CH3
Br
H

21. Achiral
 Many molecules and objects are achiral:
 identical to its mirror image
 not chiral
H H
ClCl
H H
ClCl

22. Internal Plane of Symmetry
 Cis-1,2-dichlorocyclopentane contains two
asymmetric carbons but is achiral.
 contains an internal mirror plane of
symmetry
 Any molecule that has an internal mirror plane
of symmetry is achiral even if it contains
asymmetric carbon atoms.
H H
ClCl
s

23. Internal Plane of Symmetry
 Cis-1,2-dichlorocyclopentane is a meso
compound:
 an achiral compound that contains chiral
centers
 often contains an internal mirror plane of
symmetry

24. Internal Plane of Symmetry
Example: Which of the following compounds contain
an internal mirror plane of symmetry?
C C
C
O
OH
HO H
H
Cl
HF
C C
CO2H
H
OH
H
HO
HO2C
C C
CO2H
OH
H
H
HO
HO2C
CH3H
H3C H
FF
C C
CH2CH3
Br
H
BrH
H3CH2C

25. Chiral vs. Achiral
 To determine if a compound is chiral:
 0 asymmetric carbons: Usually achiral
 1 asymmetric carbon: Always chiral
 2 asymmetric carbons: Chiral or achiral
 Does the compound have an internal plane of
symmetry?
– Yes: achiral
– No:
– If mirror image is non-superimposable,
then it’s chiral.
– If mirror image is superimposable, then it’s
achiral.

26. Conformationally Mobile Systems
 Alkanes and cycloalkanes are conformationally
mobile.
 rapidly converting from one conformation to
another
 In order to determine whether a cycloalkane is
chiral, draw its most symmetrical conformation
(a flat ring).

27. Chiral vs. Achiral
Example: Identify the following molecules as
chiral or achiral.
CH2
CH3
CH3
l
BrH
Br H
CH3 C CH2
CH3
CH3
Cl
H H
BrBr
BrH
Br H
CH3CCH2CH3
CH3
Cl
CH3CHCH2CH2CH3
Cl
C C
Br
Br
H
HCH3CH2
CH2CH3
trans-1,3-dibromocyclohexane
ethylcyclohexane

28. Mirror Planes of Symmetry
 If two groups are the
same, carbon is
achiral. (animation)
 A molecule with an
internal mirror plane
cannot be chiral.*
Notes ! If there is no plane of symmetry, molecule may be
chiral or achiral. See if mirror image can be superimposed.
Chiral molecules does Not
contain a plane of symmatry σ

29. Symmetry tests for achiral structures
 Any molecule with a plane of symmetryor a center
of symmetry must be achiral.
Achiral center: a C atom is attached by 2 or more same
groups.
---------------------------------------------------------------------Chiral
 Non-superimposable
with its mirror image
asymmetric carbon
4 different attached
groups
Enanatiomers
achiral
Superimposable
with its mirror image
plane of symmetry
2 or more same attach
groups.

30. Light that has been passed through a nicol prism or other
polarizing medium so that all of the vibrations are in the same
plane.
plane polarized light
non-polarized polarized

31. OPTICAL ISOMERISM
The polarimeter
If the light appears to have turned to the right turned to the left
DEXTROROTATORY LAEVOROTATORY
A Light source produces light vibrating in all directions
B Polarising filter only allows through light vibrating in one direction
C Plane polarised light passes through sample
D If substance is optically active it rotates the plane polarised light
E Analysing filter is turned so that light reaches a maximum
F Direction of rotation is measured coming towards the observer
A B
C D
E
F

32. Polarimeter
It is used to measure thr optical activity of a compund.

33. Specific Rotation
The angle of rotation of plane polarized ligh
t by a 1.00 gram per cm-3 sample in a 1 dm tube. [α ]D (D =
sodium lamp, λ = 589 mμ).
α
[ α ]D = where α = observed rotation
l * d
l = length (dm)
d = concentration (g/cc)
(+)-alanine [ α ]D = +8.5
(-)-lactic acid [α ]D = -3.8

34. Definitions
Optically Activity: the ability of compounds to rotate the
plane polarized light towards left or right.
Dextrorotatory (d) or (+).: an optically active compound
that rotates plane polarized light in a clockwisedirection.
Levorotatory (l) or (-): an optically active compound
that rotates plane polarized light in a
counterclockwise direction.
H
N
H
(-)-Nicotine CH3N
H3CCH3 H
(+)-Methamphetamine
N
8

35. Summary
Stereoisomers: isomers that have same formula and connectivity but
differ in the position of the atoms in space. They possess one or mor
e
stereocenters
Stereocenter: a carbon atom bearing 4 different atoms or group of
atoms.
Chiral: any moleculethat is nonsuperposable with its mirrorimage.
Enantiomers: stereoisomers that are non superposable mirror
images
Racemic mixture: a 1:1 (equimolar) mixture of two enantiomers.
Optically Active: the ability of some compounds to rotate plane polariz
ed light.

36. Biological Significance of Chirality
Since most of the natural (biological) environment consists of enantiomeric mol
ecules (amino acids, nucleosides, carbohydrates and phospholipids are chiral mo
lecules), then enantiomers will display different properties. Then, in our body
Drug
Enzyme
32
Weak BindingTight Binding
Enantiomers

37. Biological Significance of Chirality
Enantiomers
OH
of Epinephrine
H3C H3C H
H N H N
OH OHH HR SH HO
Anionic Flat area
site
OccupiedNot Occupied
Poorer Fit LessActive Better Fit More Active
33
(-)-Epinephrine(+)-Epinephrine
Flat areaAnionic
site
OH OH
Enzyme

38. Stereochemistry and Drug Action
 Why do chiral molecules react differently with biological molecules?
A A A B
C B C A
A’ A’ A’ B’
C’ B’ C’ A’
R S