Module 5
ISOMERISM AND CHIRALITY
//kdo
Isomerism and Chirality
Topic 5.1
CONSTITUTIONAL
ISOMERISM
2
Isomerism and Chirality
Isomerism
• Isomers
– Are compounds having the same numbers
and kinds of atoms but differ in the way
the atoms are arranged.
3
Isomerism and Chirality
Types of Isomers
4
Isomerism and Chirality
Constitutional (Structural) Isomers
“Different CONNECTIVITY”
• Skeletal - Different carbon skeletons
• Functional - Different functional groups
• Positional - Different position of functional groups
5
Isomerism and Chirality
Constitutional (Structural) Isomers
• Skeletal - Different carbon skeletons
butane
2-methylpropane
6
Isomerism and Chirality
Constitutional (Structural) Isomers
• Functional - Different functional groups
7
Isomerism and Chirality
Constitutional (Structural) Isomers
• Positional - Different position of functional groups
8
Isomerism and Chirality
Constitutional (Structural) Isomers
9
Isomerism and Chirality
Activity 1
• Lay a white bond paper on a flat
surface.
• Using 5 toothpicks, construct a linestructure of HEXANE, as shown below.
10
Isomerism and Chirality
Activity 1
• From this set-up, move the sticks to
make a different structure.
– No cyclic, multiple bonds or
addition/reduction of sticks
• Name it and list down on a separate
bond paper.
• Repeat until you complete five (5)
different isomers of hexane (including
hexane itself).
11
Isomerism and Chirality
Five (5) Isomers of Hexane
12
Isomerism and Chirality
Topic 5.2
CONFORMATIONAL
ISOMERISM: DRAWING
NEWMAN PROJECTIONS
13
Isomerism and Chirality
STEREOISOMERS
• Stereochemistry
– the branch of chemistry concerned with the
three-dimensional structures of molecules.
• Stereoisomers
– Same molecular formula and constitution but
different spatial (3D) arrangement of atoms
– SAME CONNECTIVITY
14
Isomerism and Chirality
Conformational Isomers
• Conformers/ Rotamers
– Different arrangement due to rotation
around a SINGLE BOND
15
Isomerism and Chirality
Activity 2
• Construct a ball and stick 3D model of
ETHANE using molding clay (atoms)
and toothpicks (bonds).
16
Isomerism and Chirality
Activity 2
• Take a snapshot after 90o of rotation (looking
directly in front of a C-C bond end on).
• On a bond paper, sketch a drawing of
ETHANE using skeletal structures (label the
H-atoms).
17
Isomerism and Chirality
Representations of Ethane
18
Isomerism and Chirality
Wedge and Dash Diagrams:
19
Isomerism and Chirality
Wedge and Dash Diagrams:
20
Isomerism and Chirality
Representations of Ethane
21
Isomerism and Chirality
Representations of Ethane
22
Isomerism and Chirality
Exercise:
• Draw the Newman projection of the given
compound, as viewed from the angle
indicated.
23
Isomerism and Chirality
FRONT:
Cl
Br
CH3
24
Isomerism and Chirality
Back:
CH3
Br
Cl
25
Isomerism and Chirality
NEWMAN PROJECTION:
Br
CH3
Br
Cl
Cl
CH3
26
Isomerism and Chirality
Exercise:
• Draw the Newman projection of the given
compound, as viewed from the angle
indicated.
27
Isomerism and Chirality
FRONT:
Cl
H
CH3
28
Isomerism and Chirality
Back:
CH3
Br
H
29
Isomerism and Chirality
NEWMAN PROJECTION:
H
CH3
Br
Cl
H
CH3
30
Isomerism and Chirality
Conformations of Ethane
• Rotate the model and take snapshots
following this diagram.
31
Isomerism and Chirality
Conformations of Ethane
• Staggered (99%):
– The lowest-energy, most stable
conformation
– all six C–H bonds are as far away
from one another as possible
• Eclipsed (1%):
– The highest-energy, least stable TORSIONAL ANGLE
conformation
– six C–H bonds are as close as
possible
32
Isomerism and Chirality
Conformations of Butane
STERIC STRAIN – REPULSION AS A RESULT OF
TRYING TO OCCUPY THE SAME SPACE
33
Isomerism and Chirality
Topic 5.3
GEOMETRIC ISOMERISM:
CIS-TRANS
ISOMERS AND THE E-Z
CONVENTION
34
Isomerism and Chirality
Activity
• Construct a ball and stick 3D model of
but-2-ene using molding clay (atoms)
and toothpicks (bonds).
35
Isomerism and Chirality
Geometric (Cis-Trans) Isomers
• Lack of rotation in C=C bonds
• For disubstituted alkenes
• Example: but-2-ene
cis-but-2-ene
trans-but-2-ene
36
Isomerism and Chirality
Exercise:
• Name the structure and assign the
configuration of double bond as either cis- or
trans-.
37
Isomerism and Chirality
Exercise:
• Name the structure and assign the
configuration of double bond as either cis- or
trans-.
trans-1,2-dibromoethene
38
Isomerism and Chirality
Exercise:
• Name the structure and assign the
configuration of double bond as either cis- or
trans-.
39
Isomerism and Chirality
Exercise:
• Name the structure and assign the
configuration of double bond as either cis- or
trans-.
cis-1,2-dibromoethene
40
Isomerism and Chirality
Geometric (Cis-Trans) Isomers
• When two identical groups are connected to
the same position, there cannot be cis-trans
isomerism.
41
Isomerism and Chirality
Example:
NOT ISOMERIC
1,1-dichloroprop-1-ene
42
Isomerism and Chirality
Exercise:
• Classify if the following structure is a
cis-, trans-, or neither an isomer.
43
Isomerism and Chirality
Exercise:
• Classify if the following structure is a
cis-, trans-, or neither an isomer.
A trans-isomer
44
Isomerism and Chirality
Exercise:
• Classify if the following structure is a
cis-, trans-, or neither an isomer.
45
Isomerism and Chirality
Exercise:
• Classify if the following structure is a
cis-, trans-, or neither an isomer.
A cis-isomer
46
Isomerism and Chirality
Exercise:
• Classify if the following structure is a
cis-, trans-, or neither an isomer.
47
Isomerism and Chirality
Exercise:
• Classify if the following structure is a
cis-, trans-, or neither an isomer.
Not isomeric
48
Isomerism and Chirality
Geometric (Cis-Trans) Isomers
• Which of the following is less stable?
cis-but-2-ene or trans-but-2-ene?
cis-but-2-ene
trans-but-2-ene
49
Isomerism and Chirality
Geometric (Cis-Trans) Isomers
• Which of the following is less stable?
cis-but-2-ene or trans-but-2-ene?
50
Isomerism and Chirality
Geometric (Cis-Trans) Isomers
• Although the interconversion of cis and trans
alkene isomers doesn’t occur spontaneously, it
can be brought about by treating the alkene with
a strong acid catalyst.
51
Isomerism and Chirality
Sequence Rules: The E,Z Designation
• With trisubstituted and tetrasubstituted double
bonds, however, a more general method is
needed for describing double-bond geometry.
• According to the E, Z system of nomenclature, a
set of sequence rules is used to assign
priorities to the substituent groups on the
double-bond carbons.
• Cahn–Ingold–Prelog rules
52
Isomerism and Chirality
Sequence Rules: The E,Z Designation
• If the higher-priority groups on each carbon are
on opposite sides of the double bond, the alkene
is designated E, for the German entgegen,
meaning “opposite.”
53
Isomerism and Chirality
Sequence Rules: The E,Z Designation
• If the higher-priority groups are on the same
side, the alkene is designated Z, for the German
zusammen, meaning “together.”
– “ze zame zide”
54
Isomerism and Chirality
Sequence Rules: The E,Z Designation
• RULE 1 Taking the double-bond carbons
separately, look at the atoms directly
attached to each carbon and rank them
according to atomic number.
– An atom with a higher atomic number is higher in
priority than an atom with a lower atomic number.
55
Isomerism and Chirality
Sequence Rules: The E,Z Designation
• RULE 2 If a decision can’t be reached by ranking the
first atoms in the substituents, look
at the
second, third, or fourth atoms away from
the double-bond carbons until the first difference is
found.
56
Isomerism and Chirality
Sequence Rules: The E,Z Designation
57
Isomerism and Chirality
Sequence Rules: The E,Z Designation
RULE 3 Multiple-bonded atoms are equivalent to the
same number of single-bonded atoms.
58
Isomerism and Chirality
Exercise:
• Assign the configuration of double bond as
either E- or Z-.
59
Isomerism and Chirality
Exercise:
(Z)- 1-bromo-2-chloro-2-fluoro-1-iodoethene
Higher
priority
Higher
priority
60
Isomerism and Chirality
Exercise:
• Assign the configuration of double bond as
either E- or Z-.
61
Isomerism and Chirality
Exercise:
• Assign the configuration of double bond as
either E- or Z-.
Higher
Higher
priority
priority
O C
H C
H C
Z-isomer
62
Isomerism and Chirality
Topic 5.4
STEREOISOMERISM:
CHIRALITY AND
SYMMETRY
63
Isomerism and Chirality
Stereochemistry
• Chemistry concerned with 3D structures
• Focus on chirality (ky-ral-i-tee), or handedness
(Greek cheir, meaning “hand”)
64
Isomerism and Chirality
Chirality
• Any object can be viewed in a mirror, revealing
its mirror image.
65
Isomerism and Chirality
Chirality
• SUPERIMPOSABLE
– The mirror image is identical to the actual object.
66
Isomerism and Chirality
Chirality
• NONSUPERIMPOSABLE
– The object and its mirror image are different.
67
Isomerism and Chirality
CHIRALITY
• Finding Handedness in Molecules
– The presence of a carbon
atom bonded to
four different groups
 stereocenter, or chirality center
68
Isomerism and Chirality
Stereocenter, or chirality center
69
Isomerism and Chirality
CHIRALITY AND SYMMETRY
• Plane of symmetry
• a plane that cuts through the middle of a
molecule or other object so that one half of
the object is a mirror image of the other
half.
• A molecule is not chiral (achiral) if it
contains a plane of symmetry.
70
Isomerism and Chirality
Which pair of figures has plane of
symmetry?
71
Isomerism and Chirality
Optical Activity
• Ability to rotate a beam of plane-polarized
light
• Polarimeter
– Measures the amount of rotation
• Some optically active molecules rotate planepolarized light
– to the right (clockwise)  Dextrorotatory (+)
– to the left (counterclockwise)  Levorotatory (-)
72
Isomerism and Chirality
Pasteur’s Discovery of Enantiomers
73
Isomerism and Chirality
Racemetes
• A.k.a. racemic (rah-see-mic) mixtures
• 50:50 mixture of enantiomers
74
Isomerism and Chirality
Chirality Centers and Stereoisomers
Maximum number of stereoisomers = 2n
– Where n = number of chirality centers
75
Isomerism and Chirality
Enantiomers
• Stereoisomers that are
nonsuperimposable mirror image
76
Isomerism and Chirality
Diastereomers
• Stereoisomers that are NOT mirror images
of each other
Meso Compounds
• Compounds that are achiral, yet contain
stereocenters
77
Isomerism and Chirality
78
Isomerism and Chirality
Topic 5.5
STEREOGENIC CENTERS
AND THE R-S
CONVENTION
79
Isomerism and Chirality
Chirality
• Objects that are not superimposable on their
mirror images are called chiral objects.
• CHIRALITY CENTER
– The most common source of molecular chirality is the presence
of a carbon atom bearing four
different groups.
– Chiral center, stereocenter, stereogenic center,
asymmetric center, CHIRAL CARBON
80
Isomerism and Chirality
Chirality
• CHIRALITY CENTER
81
Isomerism and Chirality
2-butanol
82
Isomerism and Chirality
Chirality Centers
83
Isomerism and Chirality
Exercise:
• Propoxyphene, sold under the trade name Darvon, is an
analgesic (painkiller) and antitussive (cough
suppressant). Identify all chirality centers in
propoxyphene:
84
Isomerism and Chirality
85
Isomerism and Chirality
86
Isomerism and Chirality
Answer:
87
Isomerism and Chirality
Exercise:
Identify
the chiral
carbons.
88
Isomerism and Chirality
Exercise:
Identify
the chiral
carbons.
89
Isomerism and Chirality
Enantiomers
• When a compound is chiral, it will have one
nonsuperimposable mirror image, called its
enantiomer (from the Greek word meaning
“opposite”)
90
Isomerism and Chirality
Designating Configuration Using
the Cahn-Ingold-Prelog System
RULE 1 Look at the four atoms directly
attached to the stereocenter, and assign
priorities in order of decreasing
atomic number. The atom with the
highest atomic number is ranked first;
the atom with the lowest atomic number
is ranked fourth.
91
Isomerism and Chirality
Designating Configuration Using
the Cahn-Ingold-Prelog System
RULE 2 If a decision can’t be reached by
ranking the first atoms in the
substituents, look at the second, third,
or fourth atoms outward until the first
difference is found.
RULE 3 Multiple-bonded atoms are equivalent
to the same number of single-bonded
atoms.
92
Isomerism and Chirality
1
4
2
3
93
Isomerism and Chirality
Designating Configuration Using
the Cahn-Ingold-Prelog System
Rule 4 Orient the molecule so that the group of
lowest priority (4) is pointing directly
back, away from us.
We then look at the three remaining
substituents, which now appear to radiate
toward us like the spokes on a steering
wheel (Figure 6.7).
94
Isomerism and Chirality
FRONT:
1
Cl
CH3 H2C
2
CH3
3
95
Isomerism and Chirality
Designating Configuration Using
the Cahn-Ingold-Prelog System
Priority substituent (1  2  3) is clockwise,
R configuration (Latin rectus, meaning “right”).
If an arrow from 1  2  3 is counterclockwise,
S configuration (Latin sinister, meaning “left”).
96
Isomerism and Chirality
FRONT:
1
Cl
CH3 H2C
CH3
2
3
97
Isomerism and Chirality
(S)-2-chlorobutane
98
Isomerism and Chirality
Exercise: Identify whether the structure
exhibits S- or R- configuration.
99
Isomerism and Chirality
Not
isomeric
100
Isomerism and Chirality
101
Isomerism and Chirality
102
Isomerism and Chirality
Higher
priority
103
Isomerism and Chirality
104
Isomerism and Chirality
105
Isomerism and Chirality
106
Isomerism and Chirality
Higher
priority
107
Isomerism and Chirality
Higher
priority
Higher
priority
E-isomer
108
Isomerism and Chirality
109
Isomerism and Chirality
Chirality in Nature
Just as different stereoisomeric forms of a chiral molecule
have different physical properties, they usually have
different biological properties as well. For example, the (+)
enantiomer of limonene has the odor of oranges, but the
(−) enantiomer has a piney scent.
110
Isomerism and Chirality
Chirality in Nature
111
Isomerism and Chirality
Chirality in Nature
• Fluoxetine, a commonly prescribed medication
sold under the trade name Prozac.
• Racemic fluoxetine is an extraordinarily effective
antidepressant, but it has no activity against
migraine.
• The pure S enantiomer, however, works
remarkably well in preventing migraine and is
now undergoing clinical evaluation.
112
Isomerism and Chirality
Chirality in Nature
• Why do different stereoisomers have different
biological properties?
• To exert its biological action, a chiral molecule
must fit into a chiral receptor at a target site
113
Isomerism and Chirality
- End of Presentation -
For questions, you can post them on
the discussion page in CANVAS.
114