Steriochemistry_MAMTA

Module-6
STEREOCHEMISTRY
Dr. Mamta Chahar
Department of Chemistry
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Dr. Mamta Chahar

Contents
• 3-D Representations & Isomerism
• Symmetry and chirality, enantiomers,
diastereomers,
• Optical activity, absolute configurations
• Conformational analysis
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Stereochemistry
• The branch of chemistry concerned with the
three-dimensional arrangement of atoms and
molecules and the effect of this on chemical
reactions.
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Three-Dimensional Representations
• There are four main types of representations:
(a) Wedge-Dash Projection
(b) Fisher Projection
(c)Newman Projection
(d) Sawhorse Projection.
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(a) Wedge-Dash Projection
• In this projection, a molecule in which three types of lines are used in
order to represent the three-dimensional structure:
(i) one bond is drawn coming toward you, out of the page, solid line=
wedged, represent by
(ii) one bond is drawn going away from you, behind the page, broken line =
dashed, represent by --------
(iii)one bond is drawn in the plane of paper = solid line, represent by
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(b) Fisher Projection
• In a Fischer Projection, each place where the horizontal and
vertical lines cross represents a carbon.
• Vertical lines are actually oriented away from you (similar
to dashes in the Wedge-Dash Notation)
• Horizontal lines are oriented toward you (similar to wedges in
the Wedge-Dash Notation)
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COOH
H
HO CH3

(c)Newman Projection
• Newman Projections are used mainly for determining conformational
relationships.
• In this notation, you are actually viewing a molecule by looking down a
particular carbon-carbon bond.
1) Front carbon of this bond is represented by a dot .
2) Back carbon is represented by a large circle
• The three remaining bonds are drawn as sticks coming off the dot (or
circle), separated by one another by 120 degrees.
Example
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(d) Sawhorse Projection
• Sawhorse Projection is very similar to Newman Projections.
• It is used more often because the carbon-carbon bond that is compressed in a
Newman Projection is fully drawn out in a Sawhorse Projection.
• Sawhorse Projection is a molecule down a particular carbon-carbon bond, and
groups connected to both the front and back carbons are drawn using sticks at 120
degree angles.
• Sawhorse Projections can also be drawn so that the groups on the front carbon
are staggered (60 degrees apart) or eclipsed (directly overlapping) with the
groups on the back carbon
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CONCEPT OF ISOMERISM
• Berzelius coined the term isomerism
• Greek: isos = equal; meros = part
• He describe the relationship between two clearly
different compounds having the same elemental
composition.
• Such pairs of compounds differ in their physical and
chemical properties and are called isomers.
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TYPES OF ISOMERISM
Isomerism
Structural
Stereo
Geometrical
Configurational Conformational
Optical
Chain
Positional
Functional
Metamerism
Tautomerism
Ring Chain
 Same molecular formula
 Different compound
These differ from each other in the
way their atoms are connected
differ in the manner their atoms or groups are
arranged in the space
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A. Structural or Constitutional Isomerism
• These differ from each other in the way their
atoms are connected, i.e., in their structures.
• It’s six types signifying the main difference in the
structural features of the isomers are:
I. Chain/Skeletal/Nuclear Isomerism
II. Position Isomerism
III. Functional Isomerism
IV. Metamerism
V. Tautomerism
VI. Ring Chain Isomerism
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I. Chain/Skeletal/Nuclear Isomerism
• These have same molecular formula but different
arrangement of carbon chain within the molecule. eg.
H3C- CH2- CH2-CH3 H3C—CH—CH3
n-Butane 2-Methylpropane (Isobutane)
CH3
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II. Position Isomerism
• These have same carbon skeleton but differ in
the position of attached atoms or groups or in
position of multiple (double or triple) bonds.
CH3CH2CH2O H CH3—CH—CH3
O H
Propan-1-ol Propan-2-ol
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III. Functional Isomerism
• •These have same molecular formula but
different functional groups. Eg.
CH3 CH2 O H CH3 O CH3
Ethanol Dimethyl ether
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IV. Metamerism
• These have different number of carbon atoms (or alkyl
groups) on either side of a bifunctional group (i.e., -O- , -S-, -
NH-, -COetc.).
CH3CH2—C—CH2CH3 CH3CH2CH2—C—CH3
O O
Pentan-3-one Pentan-2-one
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V. Tautomerism
• Structural isomers existing in rapid equilibrium
by migration of an atom or group are
tautomers
• It is also called as keto-enol tautomerism.
eg.
Enol form keto form
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B. STEREOISOMERISM
• Isomers which have the same molecular
formula but differ in the manner their atoms
or groups are arranged in the space are called
stereoisomers.
• It is of two types:
1) Conformational Isomerism
2) Configurational Isomerism
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1) Conformational Isomerism
• The stereoisomers which can be
interconverted rapidly at room temperature
without breaking a covalent bond are called
conformational isomers or conformers.
• Because such isomers can be readily
interconverted, they cannot be separated
under normal conditions.
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B. Configurational Isomerism
• The stereoisomers which cannot be
interconverted unless a covalent bond is
broken are called configurational isomers.
• The configurational isomerism is of two types:
a)Optical Isomerism or Enantiomerism
b) Geometrical Isomerism
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a) Optical Isomerism or Enantiomerism
• The stereoisomers which are related to each
other as an object and its non-superimposable
mirror image are called optical isomers or
enantiomers.
• Greek: enantion=opposite, mers= molecule.
• The optical isomers can also rotate the plane of
polarised light to an equal degree but in opposite
direction.
• The property of rotating plane of polarised light is
known as optical activity.
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• For example:
Molecular formula C3H6O3 represents two enantiomeric lactic acids as
shown below:
COOH COOH
H O H HO H
CH3 CH3
( -) - Lactic acid
(Rotates the plane of polarized
light towards left hand side
i.e. anticlockwise)
(+) - Lactic acid
(Rotates the plane of polarized
light towards right hand side
i.e. clockwise)
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2) Geometrical Isomerism/E–Z configuration
• Geometric isomers are the stereoisomers which differ in their
spatial geometry due to restricted rotation across a double
bond.
• These isomers are also called as cis-trans isomers.
a) If the two groups of higher priority are on opposite sides of
the double bond (trans to each other), bond is assigned the
configuration E (from entgegen, German word: opposite).
b) If the two groups of higher priority are on the same side of
the double bond (cis to each other), the bond is assigned the
configuration Z (from zusammen, German word: together).
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For example, molecular formula C2H2Cl2 corresponds to two
geometric isomers as follows:
Cl Cl Cl Cl
C C C C
H H H H
Z- (cis)-1,2-Dichloroethene E-(trans)-1,2-Dichloroethene
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The formula for determining the number of stereoisomers as follows:
a) When the molecule is unsymmetrical and contains ''n '' chiral
carbon atoms,
Total no. of stereoisomers = 2n
b) When the molecule is unsymmetrical and has even number of
stereogenic centres or chiral carbon atoms,
Total no. of stereoisomers = No. of optical isomers + No. of meso forms
= 2(n-1) + 2(n/2-1)
c) When the molecule is symmetrical and has odd no. of stereogenic
centres,
Total no. of stereoisomers = [ 2(n-1)-2(n/2-1/2)]
= [(optical active isomers)+ 2(n/2-1/2) (meso- form)]
STEREOISOMERS
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ENANTIOMERS
• Enantiomers are chiral molecules
• Non-superimposable
• Two stereoisomers that are mirror images of each other
• They show identical chemical and physical properties except
for their ability to rotate plane polarized light (+/−) by equal
amounts but in opposite directions
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Diastereomers
• They have two or more stereocenters.
• Non-superimposable on one another.
• Diastereomers are stereoisomers that are not mirror
images of one another.
• Diastereomers have different physical and chemical
properties
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Chirality
• Chirality means “handedness”.
• Every object has a mirror image, but if a molecule’s
mirror image is different from the molecule, it is said
to be a chiral molecule.
• Chiral molecules that are non-superimposable on
their mirror image.
• A tetrahedrally-bonded carbon, where all four
substituents are different, the carbon is a called
stereo-center/ chiral center. If there are two
equivalent groups on the same carbon, that carbon
cannot be a stereocenter.
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• Chiral objects: hands, feet, gloves, screws, cork screws
• Achiral objects have mirror images that are identical to
the object. A species with no chiral center - achiral
compounds have a plane or center of symmetry.
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Molecular Symmetry
1) Symmetry axis: an axis around which a rotation by 360o/n results
in a molecule indistinguishable from the original. This is also
called an n-fold rotational axis and abbreviated Cn.
Examples are the C2 axis in water and the C3 axis in ammonia.
2) Plane of symmetry: a plane of reflection through which an identical
copy of the original molecule is generated. This is also called a
mirror plane abbreviated σ.
i) A symmetry plane parallel with the principal axis is dubbed vertical (σv)
ii) one perpendicular to it horizontal (σh)
iii) A third type of symmetry plane exists: If a vertical symmetry plane
additionally bisects the angle between two 2-fold rotation axes perpendicular
to the principal axis, the plane is dubbed parallel dihedral (σd).
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Optical Activity
• It is the ability of a chiral molecule to rotate the plane of
plane-polarised light, measured using a polarimeter. A simple
polarimeter consists of a light source, polarising lens, sample
tube and analysing lens.
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• When light passes through a sample that can rotate plane polarised
light, the light appears to dim because it no longer passes straight
through the polarising filters. The amount of rotation is quantified
as the number of degrees that the analysing lens must be rotated
by so that it appears as if no dimming of the light has occurred.
Measuring Optical Activity
• When rotation is quantified using a polarimeter it is known as
an observed rotation, because rotation is affected by path length (l)
and concentration (c,). When these effects are eliminated a
standard for comparison of all molecules is obtained, the specific
rotation, [α].
[α]λ
T = 100 θ / c.l
When,
c= concentration is expressed as g sample /100ml solution
l = path length travels through a sample
θ = how much of the sample is present that will rotate the light
Specific rotation is a physical property like the boiling point of a
sample.
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• Enantiomers will rotate the plane of polarisation
in exactly equal amounts but in opposite
directions.
• Dextrorotary designated as d or (+), clockwise
rotation (to the right)
Levorotary designated as l or (-), anti-clockwise
rotation (to the left)
• If only one enantiomer is present a sample is
considered to be optically pure. When a sample
consists of a mixture of enantiomers, the effect of
each enantiomer cancels out, molecule for
molecule.
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Racemic Mixture
• 50:50 mixture of two enantiomers or a
racemic mixture will not rotate plane
polarised light.
• Optically inactive.
• A mixture that contains one enantiomer
excess, however, will display a net plane of
polarisation in the direction characteristic of
the enantiomer that is in excess.
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Racemic modification
• A mixture of equal parts of enantiomers is called a racemic
modification.
• A racemic modification is optically inactive: When
enantiomers are mixed together, the rotation caused by a
molecule of one isomer is exactly cancelled by an equal and
opposite rotation caused by a molecule of its enantiomer.
• For example, (±) -lactic acid or (±) -2-methyl-1-butanol. It is
useful to compare a racemic modification with a compound
whose molecules are superimposable on their mirror images,
that is, with an achiral compound. They are both optically
active
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Resolution
• The process of separating a racemate into pure enantiomers is
known as resolution.
• The enantiomers of the racemate must be temporarily
converted into diastereomers.
• As the physical properties of enantiomers area unit are
identical, they rarely will be separated by straightforward
physical strategies, such as half crystallization or distillation.
• Mixtures of enantiomers area unit troublesome to separate as a
result of the enantiomers has identical boiling purpose. The
technique is to convert the pair of enantiomers into a pair of
diastereomers and to utilize the different physical
characteristics of diastereomers.
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METHOD OF RESOLUTION OF
RACEMIC MODIFICATION
• Chiral reagent
• Crystallization
• Mechanical separation
• Biochemical separation
• Precipitation
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Meso compounds
• A compound with two chirality centers where
there is the same set of four groups at each
chirality center, the combination where the
four groups are arranged such that the centers
are mirror images of each other
• Molecule has an internal mirror plane- meso
compound.
• The meso compound is bisected by an
internal plane of symmetry.
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R/S Nomenclature System: Absolute configuration
(Cahn–Ingold–Prelog convention)
Priority to the four atoms attached to the stereocenters, when
assigning configuration to chirality centers.
1. Make sure you have chiral centers in the molecule. The fact that a 3-
dimensional formula is given does not imply that there are chiral
centers.
2. Assign priorities to the atoms directly attached to the chirality
center. The highest priority goes to the atom with the highest
atomic number.
H < CH3 < NH2 < OH < SH
3. In case there are isotopes, use the mass number instead, since they
have the same atomic number. eg. Incase of isotopes of hydrogen
H< D< T
Since the atomic number of hydrogen is 1, it will always be the lowest
priority group, as long as it is present.
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4. If two or more of the atoms directly attached to the chiral
center are of the same type, look at the next atom to break
the tie. Do not do this unless there is a tie. Repeat this process
until the tie is broken. It is important to emphasize that in
trying to break ties, one looks at the atoms directly attached
to the element under observation before looking at any
others. Study the examples on the following page very
carefully to make sure this point is clear.
5. If there are atoms containing double or triple bonds, count
them twice or thrice respectively. This holds for each of the
atoms involved in the double or triple bonding.
6. If the center is oriented, the lowest-priority of the four is
pointed away from a viewer, the viewer will then see two
possibilities:
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1) If the priority of the remaining three substituents decreases in clockwise
direction, it is labeled R (for Rectus =right),
2) if it decreases in counterclockwise direction, it is S (for Sinister = left)
The R / S system is an important nomenclature for representing enantiomers
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ASSIGNING ABSOLUTE CONFIGURATIONS IN FISCHER
FORMULAS
• The following points to keep in mind regarding Fischer projection formulas are:
1. Horizontal lines represent bonds to the chiral carbon that are coming out of the
plane of the paper towards the front, whereas vertical lines represent bonds going
behind the plane of the paper towards the back. Thus, Fischer formulas are easily
translated into “bow tie” formulas, which are 3-D formulas. COOH CH3 HO H
Fischer formula "Bow tie" formula HO C H COOH CH3
2. The lowest priority group bonded to the chiral carbon must always be shown as a
horizontal bond. The process of assigning (R) or (S) configuration to the chiral
carbon is the same as outlined before, but since the lowest priority group is
pointing towards the front, the configuration obtained directly from a Fischer
formula is the opposite of the actual one.
CHO CH3 HO H
1 2 3 4
The order of priorities follows a clockwise direction in the Fischer formula.
Therefore the actual configuration of this molecule is (S).
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3) Once we know the actual configuration, we can represent the
molecule in any of several possible ways using 3-D formulas. Thus
the formulas shown below all represent the same molecule as given
above in Fischer projection form. That is to say, all have the (S)
configuration at the central carbon.
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Conformational Isomerism
• Isomers, which can be interconverted just by rotations about
formally single bonds.
• Two arrangements of atoms in a molecule that differ by
rotation about single bonds -different conformations,
conformations that correspond to local minima on the energy
surface are specifically called conformational
isomers or conformers.
• Rotations about single bonds involve overcoming a rotational
energy barrier to interconvert one conformer to another.
• If the energy barrier is low, there is free rotation and a sample
of the compound exists as a mixture of multiple conformers
• If the energy barrier is high enough then there is restricted
rotation, a molecule may exist for a relatively long time period
as a stable rotational isomer or rotamers.
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Conformers of Ethane
•The ethane molecule, C2H6, can exist in two conformations
a) staggered conformations b) eclipsed conformations
a) staggered conformations: In the staggered conformation, the C-H bonds
on the rear carbon lie between those on the front carbon with dihedral
angles of 60 degrees.
 staggered conformation is slightly more stable.
b) eclipsed conformations: In the eclipsed conformation, the C-H bonds on the
front and back carbons are aligned with each other with dihedral angles of 0
degrees.
 In the eclipsed form, the electron densities on the C-H bonds are closer
together than they are in the staggered form.
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Energy Profiles for Ethane
On the graph, the minima- staggered conformations and
maxima- eclipsed conformations.
Order of Stability of conformers:
Staggered> Eclipsed
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Conformers of Butane
• Butane has mainly following conformers:
a) Anti Conformation- (C–C–C–C torsion angle) ΦCCCC = 1800
b) Gauche conformation- two gauche conformations defined by ΦCCCC = 600
c) Eclipse comformation- ΦCCCC = 00
d) Partially Eclipse comformation
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Energy Profiles for Butane:
Order of Stability:
• Anti> Gauche> Partially eclipse> Fully Eclipse
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• SUBSCRIBE YOUTUBE CHANNEL:
Dr. Mamta Chahar
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References
• O. P. Agrawal- Organic Chemistry Reaction
and Reagent, 2012.
• Ernest N. Eleil, Stereochemistry of carbon
compounds
• Jerry March
• D. Nasipuri
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All the Best!
Dr. Mamta Chahar 53

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