CHAPTER THREE
STEREOCHEMISTRY
6/25/2024 By: Fikadu Girma
Introduction
The study of molecules as three-dimensional objects is called
Stereochemistry.
Objects that are not superposable on their mirror images are
said to be chiral. In other words, its mirror image is not the
same as itself.
In contrast, when an object and its mirror image are
superposable (same), the object is achiral.
Chirality is a property of the entire molecule, whereas a
chirality center is the cause of chiral (Not always).
The most common cause of chirality in organic molecules is a
tetrahedral atom, most commonly carbon, bonded to four
different groups and is called a chiral center.
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Cont.….
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Cont.….
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Optical isomerism
Isomers having the same molecular formula but different
spatial arrangement of their atoms are called stereoisomer.
An optically active compounds exists in two isomeric forms
and are called optical isomers.
Those rotate the plane polarized light equal in magnitude but
opposite in direction.
This phenomena is called Optical Activity.
The equimolar mixture of two isomers do not rotate the plane
polarized light at all and is said to be racemic mixture.
Optical isomers have the same physical properties like:
Melting point, boiling point, density etc.
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Cont.….
Optical isomers that are mirror images are called enantiomers.
They represent two optical isomers as dextrotatory (+), and
levorotatory (-).
Their opposite rotatory powers are due to the opposite
arrangements of groups around a chiral carbon.
The device that is used for measuring the effect of optically
active compounds on plane-polarized light is a polarimeter.
If the polarimeter is empty or if an optically inactive substance
is present, the axes of the plane polarized light and the
analyzer will be exactly parallel when the instrument reads 0°.
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Polarimeter
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Configurations of Chiral Centers
Chemists use the letters R and S to indicate the configuration
about an asymmetric carbon.
For any pair of enantiomers with one asymmetric carbon, one
will have the R configuration and the other will have the S
configuration.
The R,S system was devised by Cahn, Ingold, and Prelog.
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Cont.….
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Cont.….
5. Trace from group 1 to 2 to 3 to 4:
Clockwise = R
Counterclockwise = S
If the group (or atom) with the lowest priority is bonded by a
hatched wedge, draw an arrow from the group (or atom) with
the highest priority 1 to the group (or atom) with the second
highest priority 2.
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Cont.….
If the group with the lowest priority (4) is not bonded by a
hatched wedge, then switch two groups so group 4 is bonded
by a hatched wedge.
So if the arrow points clockwise, the enantiomer (with the
switched groups) has the R configuration, which means the
original molecule has the S configuration and vice versa.
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Fischer Rules
Carbon chain is on the vertical line.
Highest oxidized carbon ( carbon number 1) is at top.
Rotation of 180 degree in plane doesn’t change molecule.
Do not rotate 90 degree.
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Fischer Projections
Flat representation of a 3-D molecule.
A chiral carbon is at the intersection of horizontal & vertical.
Horizontal lines are forward, out-of-plane.
Vertical lines are behind the plane.
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R,S-configurations to Fischer projections
Rank the groups (or atoms) that are bonded to the asymmetric
carbon in order of priority.
Draw an arrow from the group with the highest priority 1 to
the group (or atom) with the next highest priority 2.
If the arrow points clockwise, the enantiomer has the R
configuration and vice versa, provided that the group with the
lowest priority (4) is on a vertical bond.
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Cont.….
If the group (or atom) with the lowest priority is on a
horizontal bond, the configuration you get from the direction
of the arrow will be the opposite.
If the arrow points clockwise, suggesting that the asymmetric
carbon has the R configuration, it actually has the S
configuration and vice versa.
In the following example, the group with the lowest priority is
on horizontal bond.
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Properties of enantiomers
Enantiomers always exist in pair.
Enantiomers are non-super imposable mirror image to each
other.
Enantiomers have same physical properties (like boiling point,
melting point, solubility, density.
Each enantiomers have opposite behavior with respect to
plane polarized light.
Each enantiomers shows the same chemical reactivity with
achiral reagent; however they have different reactivity with
chiral reagent.
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Symmetry and dissymmetry
All optically active molecules/object are chiral.
Elements of symmetry are a simple tool to identify whether a
molecule is chiral or not.
The necessary condition for optically active molecule to be
chiral is that, the molecule should not possess any kind of
symmetry elements. Like:
Plane of symmetry (σ)
Centre of symmetry (Ci)
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Cont.….
1. Plane of symmetry (σ) :
A molecule is said to possess a plane of symmetry if the atoms
or groups on one side of the plane forms the mirror image of
those on the other side.
In other words, a plane which bisects a molecule/object in two
equal halves.
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Cont.….
2. Centre of symmetry (Ci)
A center of symmetry in a molecule is said to exist:
If a line is drawn from any atom or group to this point and
then extended to an equal distance beyond this point meets
the identical atom or group.
A center of symmetry is usually present only in an even
membered ring.
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Diastereomers
Diastereomers are stereoisomers that are not mirror images of
each other.
The term diastereomers refers to a relationship between a pair
of objects.
It is important to note that diastereomers can be chiral or
achiral objects but that enantiomers must be chiral objects.
Diastereomers will arise whenever there are two or more
chiral centers present in a molecule.
As a general rule, a molecule with n chirality centers can have
maximum up to 2n stereoisomers.
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Cont.….
Enantiomers have opposite configurations at all chirality
centers, whereas diastereomers have opposite configurations
at some chirality centers but the same configuration at others.
Diastereomers have different physical properties like: melting
points, boiling points, solubility's, and different chemical
properties they react with the same achiral reagent at different
rates.
Example:
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Cont.….
Solution:
Exercise
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Meso Compounds
We have seen that each compound with n asymmetric carbons
has 2n stereoisomers.
However, some compounds with two asymmetric carbons
have only three stereoisomers.
This is why we emphasized in that the maximum number of
stereoisomers is 2n instead of stating that a compound with n
asymmetric carbons has 2n stereoisomers.
Compounds that are achiral, yet contain chirality centers, are
called Meso compounds.
Meso compounds are not optically active.
If a compound has a plane of symmetry, it will not be optically
active even though it has asymmetric carbons.
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Cont.….
A Meso-compound requires at least two chiral centers.
These must also have different absolute configurations.
If both of two chiral centers have the same absolute
configurations, then each half would no longer be a mirror
image of the other half and the compound would no longer be
a Meso-compound.
An example of a compound with two asymmetric carbons that
has only three stereoisomers is 2,3-dibromobutane.
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Cont.….
Meso cpd 1 and its mirror image are the same molecule.
If you look either at the perspective formulas drawn in their
eclipsed conformations or at the Fischer projections.
To convince yourself that the Fischer projection of 1 and its
mirror image are identical, rotate the mirror image by 180°.
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Cont.….
A compound with the same groups bonded to two different
asymmetric carbons will have three stereoisomers.
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Conformational isomerism
Isomers that differ as a result of sigma bond rotation of C-C
bond in alkanes called Conformational isomerism.
Alkanes of two or more carbons can be twisted into a number
of different three dimensional arrangements of their atoms by
rotating about one or more carbon-carbon bonds.
Ball-and-stick model of a staggered conformation of ethane.
In this conformation, the three C-H bonds on one carbon are
as far apart as possible from those bonds on the adjacent
carbon.
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Cont.….
Newman projection for an eclipsed conformation of ethane.
In this conformation, the three C-H bonds on one carbon are
as close as possible to the three C-H bonds on the adjacent
carbon.
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Cont.….
Torsional Strain: Strain on a molecule caused by bond
opposition, electron repulsion between eclipsing bonds.
Steric Strain: Repulsion between atoms and groups
The higher the strain, the less stable the conformation.
Eclipsed conformations are less stable than staggered
conformations. Because that torsional strain is high in eclipsed
confirmations.
The bonds on the front and back carbons are close to each
other and repel each other destabilizing the molecule.
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Cycloalkanes
The structures and energies of cyclic alkanes are highly
dependent on the size of their rings.
Cyclohexane: Adopts a number of puckered conformations
that interconvert via C-C rotations, the most stable of which is
the chair conformation.
In this conformation, all C-C-C bond angles are 110.98
(minimizing angle strain) and all hydrogen's on adjacent
carbons are staggered with respect to one another (minimizing
torsional strain).
In addition, no two atoms are close enough to each other for
non-bonded interaction strain to exist.
So, there is little strain in a chair conformation of
cyclohexane.
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Cont.….
Example:
Equatorial bonds are approximately perpendicular to the
imaginary axis and form an equator about the ring.
Axial bonds are parallel to the imaginary axis.
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Cis,Trans isomerism in Cycloalkanes
Cycloalkanes with substituents on two or more carbons of the
ring show a type of stereoisomerism called Cis, trans isomer.
End
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