Organic Chemistry -Unit II

B.Sc. Semester 2

Prepared by
Rojo John
Dept. of Chemistry
SFS College
Stereochemistry refers to the
3-dimensional properties and
reactions of molecules.
 ISOMERISM
Isomers are different compounds with the same
molecular formula. CHAIN ISOMERISM

STRUCTURAL ISOMERISM POSITION ISOMERISM

Same molecular formula but

different structural formulae FUNCTIONAL GROUP
ISOMERISM

STEREOISOMERISM
Same molecular
formula but atoms
occupy different
positions in space.
GEOMETRICAL ISOMERISM
Occurs due to the restricted
rotation of C=C double bonds...
two forms - CIS and TRANS
OPTICAL ISOMERISM
Occurs when molecules have a
chiral centre. Get two non-
superimposable mirror images.
Are the following pairs of compounds structural isomers or
stereoisomers?
a)
structural

b)
structural

c)
stereoisomer

5
 Asymmetric carbon –Tetrahedral carbons
with 4 different groups attached
 Itsmirror image will be a different compound
(enantiomer).

 Asymmetric carbon/chiral centre /chirality

centre/ stereocentre /stereogenic centre
 Symmetry elements are geometric
entities about which a symmetry operation
can be performed.
 Axisof symmetry
 Plane of symmetry
 Center of symmetry
 Water has a 2-fold axis
of rotation. When
rotated by 180o, the
hydrogen atoms change
their places, but the
molecule will look
exactly the same.
 n-fold rotation - a rotation of 360°/n about the Cn axis (n = 1 to )

O(1) 180° O(1)

H(2) H(3) H(3) H(2)

Molecule appears unchanged

H(3) H(4)
H(2)

120° 120°
N(1) N(1) N(1)

H(2) H(4) H(3) H(2)

H(4) H(3)

In ammonia there is a C3 axis so we can perform 3-fold (120°) rotations to get

identical arrangement of atoms.
 Ammonia has a C3 axis.
Rotation by 120o in a clockwise or
a counterclockwise direction
provide two different
orientations of the molecule.
A plane of symmetry is a mirror plane that cuts
the molecule into two equal halves, so that one
half of the molecule is a reflection (mirror image)
of the other half. The presence of a plane of
symmetry makes a molecule achiral.

Cl
Br
H H
H F
 3. Centre of symmetry
If any straight line passes an atom and molecular
center, the same atom or group is encountered
on the site at equal distance but in the opposite
direction.
Ex. trans-2,4-dichloro-1,3-difluorocyclobutane
F Cl
Centre of symmetry
H H
H H

Cl F
 Optical activity – the ability to rotate the
plane of plane –polarized light
 Chiral compound – a compound that is
optically active
 achiral compound will not rotate light
 Polarimeter – device that measures the
optical rotation of the chiral compound
Plane-Polarized Light through an Achiral Compound

• With achiral compounds, the light that exits the sample

tube remains unchanged. A compound that does not
change the plane of polarized light is said to be optically
inactive.

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 Plane-Polarized Light through a Chiral Compound
• With chiral compounds, the plane of the polarized light is
rotated through an angle . The angle  is measured in
degrees (°), and is called the observed rotation. A
compound that rotates polarized light is said to be optically
active.

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 Use monochromatic light, usually sodium D
 Movable analyzing filter to measure angle
 Clockwise = dextrorotatory = d or (+)
 Counterclockwise = levorotatory = l or (-)
 Not related to (R) and (S)

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Chiral and Achiral Molecules
• Although everything has a mirror image, mirror images
may or may not be superimposable.
• Some molecules are like hands. Left and right hands are
mirror images, but they are not identical, or
superimposable.

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 A molecule or object that is not superimposable
on its mirror image is said to be chiral.
 A molecule or object that is superimposable on
its mirror image is said to be achiral.
• We can now consider several molecules to determine
whether or not they are chiral.

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The molecule labeled A and its mirror image labeled B are
not superimposable. No matter how you rotate A and B, all
the atoms never align. Thus, CH3CHOHCH2CH3 (2-
butanol)is a chiral molecule, and A and B are different
compounds.
• A and B are stereoisomers—specifically, they are
enantiomers- stereoisomers which are
nonsuperimposable mirror images of each other.

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stereoisomers which are
nonsuperimposable mirror images of each
other.

 Stereoisomers that are not mirror images.

 Molecules with 2 or more chiral carbons.

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 Enantiomers:
I & II

I II Diastereomers
I & III and II & III

III IV
 Same boiling point, melting point, density
 Same refractive index
 Same interaction with achiral molecules
 Different direction of rotation in polarimeter
 Enantiomers are difficult to separate
 Different interaction with other chiral molecules
 Enzymes
 Taste buds, scent

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 Diastereomers have different physical properties
like m.p., b.p.
 They can be separated easily.
 Their rotation of plane polarized light may be
same or different.
 Their chemical reactivity is different.

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 No. of stereoisomers = 2n
n= no. of chiral centers
* CH3
H
CH H * *
3
* *
* * H *H
HO
H

Cholesterol: eight chiral centers

28 = 256 possible stereoisomers
(only one of which is naturally occurring)
 GEOMETRICAL ISOMERISM IN ALKENES
Introduction

• an example of stereoisomersim
• found in some, but not all, alkenes
• occurs due to the RESTRICTED ROTATION OF C=C bonds

CIS TRANS
Similar groups/atoms are on the Similar groups/atoms are on
SAME SIDE of the double bond OPPOSITE SIDES of the double
bond
Isomers - have different physical properties - e.g. boiling points, density
- have similar chemical properties - in most cases
 GEOMETRICAL ISOMERISM

RESTRICTED ROTATION OF C=C BONDS

Single covalent bonds can easily rotate. What appears to be a different structure in an
alkane is not. Due to the way structures are written out, they are the same.

ALL THESE STRUCTURES ARE THE SAME BECAUSE C-C BONDS HAVE ‘FREE’ ROTATION
 GEOMETRICAL ISOMERISM

RESTRICTED ROTATION OF C=C BONDS

C=C bonds have restricted rotation. So the groups on either end of the bond are
‘frozen’ in one position; it isn’t easy to flip between the two.

This produces two possibilities. The two structures cannot interchange easily
so the atoms in the two molecules occupy different positions in space.
 GEOMETRICAL ISOMERISM

How to tell if it exists

Two different Two different

atoms/group
s attached
atoms/group
s attached  GEOMETRICAL ISOMERISM


Two similar Two similar
atoms/group atoms/group
Once you get two similar
s attached s attached
atoms/groups attached to
one end of a C=C, you
cannot have geometrical


Two similar Two different
atoms/group atoms/group isomerism
s attached s attached

Two different Two different

atoms/group
s attached
atoms/group
s attached  GEOMETRICAL ISOMERISM
Cis-trans isomers are not mirror images, so
these are diastereomers.

H H H CH3
C C C C
H3C CH3 H3C H
cis-2-butene trans-2-butene

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 Cl Br
C C
H F
hat is needed:
1) systematic body of rules for ranking substituents
2new set of stereochemical symbols other than cis and
trans
 The E-Z Notational System
 E :higher priority substituents on opposite sides
 Z :higher priority substituents on same side

higher lower higher higher

C C C C

lower higher lower lower

Entgegen Zusammen
 Configuration
• Structures that can be interconverted
only by breaking one or more bonds.
• Changing the configuration of a
molecule always means that bonds
are broken
• • A different configuration is a
different molecule
 Relative Configuration
D and L Assignments
CHO
H OH
CHO
*
CH2OH H OH
D-(+)-glyceraldehyde
HO H
COOH H OH
H2N H H * OH
*
CH2CH2COOH
CH2OH
L-(+)-glutamic acid
D-(+)-glucose
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 Fischer Projections
• Flat drawing that represents a 3D molecule
• A chiral carbon is at the intersection of
horizontal and vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.

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 Racemic Mixtures

• Equal quantities of d- and l- enantiomers.

• Notation: (dl) or ()
• No optical activity.
• The mixture may have different b.p. and m.p.
from the enantiomers!

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Chapter 5 39
 Absolute Configuration
The R,S system of nomenclature
Cahn-Ingold-Prelog Rules
Rank the groups (atoms) bonded to the chirality center

• Atom with highest atomic

number assigned the highest
priority #1.
• In case of ties, look at the next
atoms along the chain.
• Double and triple bonds are
treated like bonds to duplicate
atoms.
Orient the lowest priority (4) away from you

Draw an arrow from highest to

lowest priority group.

Clockwise = R configuration

Counterclockwise = S configuration
Discrimination of Enantiomers by
Biological Molecules
 Biological Discrimination

Epinephrine (also known as adrenalin) is a hormone and a

neurotransmitter.
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Rotation of the Projection 90o
Reverses Absolute Configuration
 Meso Compounds
Have two or more asymmetric carbons and a plane of
symmetry

They are achiral molecules(optically inactive)

 CH3 CH3 H H
H2, Pt/C
CH3 CH3
CH2CH3 CH2CH3 CH2CH3 CH2CH3

CH2CH3 product is meso

H CH3
H CH3
CH2CH3
 Conformational Isomerism
Conformations - Different spatial
arrangements that a molecule can adopt
due to rotation about sigma bonds

Rotation about
Carbon–Carbon
Bonds
 Conformational Analysis
Drawing Acyclic Molecules

• Newman Projections
Conformational Analysis of Ethane

• Sawhorse Drawings
 Different Conformations of Ethane

• A staggered conformer is more stable than an eclipsed

conformer
60o Rotation Causes Torsional or Eclipsing Strain

• Torsional strain: repulsion between pairs

of bonding electrons
Conformations of n-Butane
(C2-C3)
PE Diagram for n-Butane
2 Different Eclipsed Conformations
Strain Energy can be Quantified
Butane has Steric and Torsional Strain When
Eclipsed

• Steric strain: repulsion between the electron

clouds of atoms or groups
 Cycloalkanes: Ring Strain
• Angle strain results when bond angles deviate from the
ideal 109.5° bond angle( tetrahedral).
The Shapes of Cyclohexane:
Planar or Non-planar?

Tetrahedral bond angles

require non planar
geometries.
Cyclohexane

In reality, cyclohexane adopts a puckered “chair” conformation, which

is more stable than any possible other conformation.

The chair conformation is so stable because it eliminates angle strain

(all C—C—C angles are 109.5°), and torsional strain (all hydrogens on
adjacent C atoms are staggered).

61
Types of Strain
• Torsional strain
strain that results from eclipsed bonds
(measure of the dihedral angle)
• Van der Waals strain or (Steric strain)
strain that results from atoms being too
close together.
• Angle strain results from distortion of bond
angles from normal values, for a
tetrahedron 109.5o
•The chair conformation of cyclohexane is free of strain
Chair Conformation
Boat Conformation
Chair is the most stable
conformation of cyclohexane

 All of the bonds are staggered and the bond

angles at carbon are close to tetrahedral.
 Boat conformation is less stable
than the chair
180 pm

 All of the bond angles are close to tetrahedral but close

contact between flagpole hydrogens causes strain in
boat.
 Boat conformation is less
stable than the chair

 Eclipsed bonds bonds gives torsional strain to boat.

Skew boat is slightly more stable
than boat
Boat Skew or Twist Boat

 Less van der Waals strain and less torsional strain in

skew boat.
 Axial and Equatorial
Bonds in Cyclohexane
Drawing Cyclohexane
The 12 bonds to the ring can be
divided into two sets of 6.
 6 Bonds are axial

Axial bonds point "north and south"

6 Bonds are equatorial

Equatorial bonds lie along the equator

 Figure 4.12
A three-dimensional model of
the chair form of cyclohexane
with all H atoms drawn

75
Ring-Flipping in
Cyclohexane
just by rotating bonds (that is, without breaking any!)
cyclohexane can ring invert or ‘flip’. After ring
inversion has taken place, all the bonds that were
axial are nowequatorial and vice versa.
 Conformational Inversion

chair-chair interconversion (ring-flipping)

rapid process (activation energy = 45 kJ/mol)
all axial bonds become equatorial and vice ve
Half chair
Half chair

Twist boat
Half-
chair

Twist boat
Half-
chair

Twist
boat
45 45
kJ/mol kJ/mol

23
kJ/mol
The Conformations of Cyclohexane
and Their Energies
Cyclohexane
Chair Conformation
Boat Conformation
How to Draw a
Chair Conformation

all opposite bonds

are parrallel
Axial bonds and
Equatorial bonds
Rings can Flip from one Chair
Conformation to Another
 Flipping Chair Conformations
• All axial bonds become equatorial
• All equatorial bonds become axial
• All “up” bonds stay up
• All “down” bonds stay down
axial up

eq. up
 Naming from the Perspective Formula
1. Rank the groups bonded to the asymmetric carbon
1

2
3

2. If the group (or atom) with the lowest priority is

bonded by hatched wedge,
3. If necessary, rotate the molecule so that the lowest
priority group (or atom) is bonded by a hatched wedge

4. You can draw group 1 to group 2, passing group 4,

but never 3
 Naming from the Fischer Projection
1. Rank the groups (or atom) that are bonded to the asymmetric
carbon and draw an arrow with the highest priority to the lowest
priority
Cl

CH3CH2 CH2CH2CH3
(R)-3-chlorohexane
H
2. If the lowest priority is on a horizontal bond, the naming is
opposite to the direction of the arrow
CH3

H OH (S)-2-butanol
CH2CH3
3. The arrow can go from group 1 to 2, passing group 4, but not
group 3
CO2H

H CH3
(S)-lactic acid
OH

A Fischer projection can only be rotated 180° in the plane

of the paper to yield the same molecule
104
More Slides
Rings can Flip from one Chair
Conformation to Another
 Flipping Chair Conformations
• All axial bonds become equatorial
• All equatorial bonds become axial
• All “up” bonds stay up
• All “down” bonds stay down
axial up

eq. up
 Naming from the Perspective Formula
1. Rank the groups bonded to the asymmetric carbon
1

2
3

2. If the group (or atom) with the lowest priority is

bonded by hatched wedge,
3. If necessary, rotate the molecule so that the lowest
priority group (or atom) is bonded by a hatched wedge

4. You can draw group 1 to group 2, passing group 4,

but never 3
 Naming from the Fischer Projection
1. Rank the groups (or atom) that are bonded to the asymmetric
carbon and draw an arrow with the highest priority to the lowest
priority
Cl

CH3CH2 CH2CH2CH3
(R)-3-chlorohexane
H
2. If the lowest priority is on a horizontal bond, the naming is
opposite to the direction of the arrow
CH3

H OH (S)-2-butanol
CH2CH3
3. The arrow can go from group 1 to 2, passing group 4, but not
group 3
CO2H

H CH3
(S)-lactic acid
OH

A Fischer projection can only be rotated 180° in the plane

of the paper to yield the same molecule
113
Labeling Stereogenic Centers with R or S

114
 Designation of absolute configuration
1. Rank the substituents according to
Cahn-Ingold-Prelog rule.
CH3
C H OH > CH2CH3 > CH3 > H
HO
CH2CH3 2-Butanol
2. Orient the molecule so that the lowest
ranked substituent points away from you.
CH3
H
Et OH
116
117
Label each compound as R or S.
a) Cl 2 2

H
S
H3C Br 3 1
3 1

b) CH2Br
rotate
CH2Br
2
2

ClH2C H3C
OH CH2Cl
H3C HO
1 3 1 3
R

118
Labeling Stereogenic Centers with R or S

121
 Designation of absolute configuration
1. Rank the substituents according to
Cahn-Ingold-Prelog rule.
CH3
C H OH > CH2CH3 > CH3 > H
HO
CH2CH3 2-Butanol
2. Orient the molecule so that the lowest
ranked substituent points away from you.
CH3
H
Et OH
123
 Figure 5.7
Examples: Orienting the lowest
priority group in back

124
Label each compound as R or S.
a) Cl 2 2

H
S
H3C Br 3 1
3 1

b) CH2Br
rotate
CH2Br
2
2

ClH2C H3C
OH CH2Cl
H3C HO
1 3 1 3
R

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