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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