Isomerism and Stereoisomery

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 Two main classes of ISOMERS
Isomers are different compounds with the same molecular
formula

• The two main classes of isomers are constitutional isomers and

stereoisomers.

• Constitutional (or structural) isomers have different IUPAC names,

equal or different functional groups, different physical properties,
and different chemical properties.

• Stereoisomers differ only in the way atoms are arranged in space.

They have identical IUPAC names (except for the cis or trans prefix)
and same functional groups.

• A particular three-dimensional arrangement is called configuration.

Thus, stereoisomers have different configurations.

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Comparison between constitutional isomers
and stereoisomer

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 Chirality
• Although each object has its own mirror image, mirror
images may or may not superimposable.
• Some molecules are like hands: the right hand and the
left hand are one mirror image of the other, but they are
not identical, or superimposable.

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 Achiral molecules
• Other molecules are like chairs.
Two chairs form a pair of mirror
images that are
superimposable. A chair and its
mirror image are therefore
identical.

• A molecule or an object that

can be superimposed on its
mirror image is called achiral.

• A molecule or object that

cannot be superimposed on its
mirror image is called chiral.

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 Achiral Compounds

Take this mirror image and try to superimpose it on the one to the left matching all
the atoms. Everything will match.

When the images can be superimposed the compound is

achiral.
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 Planes of Symmetry

A molecule that has a plane of symmetry is achiral.

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Let’s consider some molecules to determine
whether they are chiral or not.

CH2BrCl

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Tetrahedral carbon atoms and their
mirror images. Molecules of the type
CH3X and CH2XY are identical to
their mirror images, but a molecule of
the type CHXYZ is not.
A CHXYZ molecule is related to its
mirror image in the same way that a
right hand is related to a left hand.

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 Chiral Carbons

❑ Carbons with four different groups attached are chiral.

❑ Its mirror image will be a different compound enantiomer –

nonsuperimposable mirror image.

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 A carbon atom bound to four different
groups is a tetrahedral stereogenic
center
• Molecule A and its mirror image B cannot be superimposed. No matter
how A and B are rotated, it will never be possible to superimpose all of
their atoms.

• A and B are stereoisomers - more precisely they are enantiomers.

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Summary of the Basic Principles of Chirality:

• Each object has its own mirror image. The fundamental

question is whether a molecule and its mirror image are
superimposable.
• If a molecule and its mirror image are nonsumperimposable,
the molecule and its mirror image are chiral.
• The terms stereogenic center and chiral molecule are
related but distinct. In general, a chiral molecule must have
one or more stereogenic centers.
• In general, a molecule without stereogenic centers is not
chiral. However, there are some exceptions to this
generalization.

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• With a tetrahedral stereogenic center, the molecule is
always chiral.

• With two or more stereogenic centers, a molecule may or

may not be chiral.

• Achiral molecules contain a plane of symmetry, while

chiral molecules do not.

• A plane of symmetry is a plane that cuts the molecule in

half, so that one half is the reflection of the other.

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 Stereogenic centers on C that are not
part of a cycle
• To identify a stereogenic center, consider each tetrahedral carbon of
a molecule and look at the four groups - not the four atoms - bound
to it.
• Never include all C atoms that cannot be tetrahedral stereogenic
centers. These include:
❖ groups CH2 and CH3
❖ any C hybridized sp or sp2.

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Larger organic molecules can have two, three or even a
hundred stereogenic centers.

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 How to draw a pair of enantiomers
• To draw both enantiomers of a chiral compound, such as 2-butanol,
use the typical convention to represent the tetrahedron:
- two bonds in the plane
- one above the plane (wedge) → towards the viewer
- one behid the plane (dashed) → away from the viewer

Then, to form the first enantiomer, arrange the groups H, OH, CH3 and
CH2CH3, arbitrarily, on each bond of the stereogenic center. Then draw
its mirror image.

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 Stereogenic centers in cyclic molecules
• Carbon atoms that are part of a ring can be stereogenic centers.
• To find the stereogenic centers on the ring carbons, always draw
the loop as a flat polygon, and look for the tetrahedral carbons
that are related to four different groups.

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In 3-methylcycloesene, the substituents CH3 and H, which
are above and behind the ring plane, are drawn with
wedges and dashed lines.

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Many biologically active compounds contain one or more
stereogenic centers on ring carbons.

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 (R) And (S) Nomenclature

• Since enantiomers are two different compounds, they must have

different names.
• The nomenclature of enantiomers with prefixes R or S is called the Cahn-
Ingold-Prelog system.
• Usually only one enantiomer will be biologically active.
• Configuration around the chiral carbon is specified
with (R) and (S).

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 (R) And (S) Nomenclature
• Since enantiomers are two different compounds, they must
have different names.
• The nomenclature of enantiomers with prefixes R or S is
called the Cahn-Ingold-Prelog system.
• To draw an enantiomer such as R or S, priority must first be
given to each group linked to the stereogenic center, based
on the descending atomic number. The atom with the
highest atomic number has the highest priority (#1).

R = clockwise
S = counter-clockwise

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 Cahn–Ingold–Prelog Rules

❑ Assign a priority number to each group attached

to the chiral carbon.
❑ Priority is assigned according to atomic
number. The highest atomic number assigned is
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.

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❑ If two atoms on a stereogenic center are equal, assign
priority based on the atomic number bound to these
atoms. A higher atomic number determines higher
priority.

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❑ To assign priority to an atom that is part of multiple bonds, consider
as if it were bound with an equivalent number of single bonds. For
example, the C of a group C=O is considered to be bound by a single
bond to two atoms of O.

❑ Other types of recurring multiple bonds are given below:

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Treatment of Multiple Bonds

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Examples of priority assignments to
stereogenic centres

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 Assign Priorities

Atomic number: F > N > C > H

Once priorities have been assigned, the lowest priority

group (#4) should be moved to the back if necessary.

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 Assign Priorities

Counterclockwise
(S)

Draw an arrow from Group 1 to Group 2 to Group 3 and

back to Group 1. Ignore Group 4.

Clockwise = (R) and Counterclockwise = (S)

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 Example

3
CH3

1
CH3CH2CH=CH H4
CH2CH2CH2CH3
2

Counterclockwise
(S)

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 In-class problem
1. Draw the enantiomers of 1,3-dibromobutane and label them as (R) and
(S). (Making a model is particularly helpful for this type of problem.)

Solution
The third carbon atom in 1,3-dibromobutane is asymmetric. The bromine atom receives first
priority, the (–CH2CH2Br) group second priority, the methyl group third, and the hydrogen
fourth. The following mirror images are drawn with the hydrogen atom back, ready to assign
(R) or (S) as shown.

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 In-class problem
2. Star (*) each asymmetric carbon in the following examples, and
determine whether it has the (R) or (S) configuration.

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 In-class problem: solutions
2. Star (*) each asymmetric carbon in the following examples, and
determine whether it has the (R) or (S) configuration.

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 In-class problem
3. Name the following alkanes and label them as (R) or (S)

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 In-class problem: solutions
3. Name the following alkanes and label them as (R) or (S)

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 Properties of Enantiomers

▪ Same boiling point, melting point, and density.

▪ Same refractive index.
▪ Rotate the plane of polarized light in the same magnitude,
but in opposite directions.
▪ Different interaction with other chiral molecules:
▪ Active site of enzymes is selective for a specific
enantiomer.
▪ Taste buds and scent receptors are also chiral.
Enantiomers may have different smells.

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 Optical Activity
Enantiomers rotate the plane of polarized light in opposite
directions, but same number of degrees.

Clockwise Counterclockwise
Dextrorotatory (+) Levorotatory (-)
Not related to (R) and (S)

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 Racemic Mixtures

• Equal quantities of d- and l- enantiomers.

• Notation: (d,l) or ()
• No optical activity.
• The mixture may have different boiling point (b.
p.) and melting point (m. p.) from the
enantiomers!
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 Diastereoisomers

• For a molecule with n stereogenic centers, the maximum

number of stereoisomers is 2n.

Let’s consider a step procedure to find all possible stereoisomers of 2,3-

dibromopenthane.

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• If the compound and its mirror image have been written correctly,
only two things need to be done to see if the atoms align: place B
directly on A, then rotate B to 180° to see if the atoms align with
A.

• In this case the atoms of A and B do not align, and therefore A

and B are two of the four possible stereoisomers of 2,3-
dibromopenthane.

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• By exchanging the position of H and Br (or two other groups) on
the stereogenic center of A (or B) a new stereoisomer is formed
(denoted by C), which is different from both A and B. The mirror
image of C is denoted by D. C and D are enantiomers.

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 Summary: the four stereoisomers of 2,3-dibromopenthane

• Stereoisomers that are not mirror images of each other are

diastereoisomers. For example, A and C are diastereoisomers.

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 Meso compounds
• Consider the stereoisomers of 2,3-
dibromobutan. Since this molecule has
two stereogenic centers, the maximum
number of stereoisomers is 4.

• To find all the stereoisomers of 2,3-dibromobutan, arbitrarily add the

groups H, Br and CH3 to the stereogenic centers, thus forming the
stereoisomer A, and then draw its mirror image B.

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• To find the other two stereoisomers (if any), exchange the
positions of the two groups on the same stereogenic center of a
single enantiomer. In this case, by exchanging the position of H
and Br on a stereogenic center of A, it forms C, which is different
from both A and B.

• A meso compound is an achiral compound that contains

tetrahedral stereogenic centers. C is a meso compound.

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• Compound C contains a plane of symmetry, and therefore is
achiral.
• Meso compounds contain a plane of symmetry, and therefore are
characterized by two identical halves.

• Since a 2,3-dibromobutan stereoisomer is superimposed on its

mirror image, there are only three stereoisomers, not four.

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Summary: the three stereoisomers
of 2,3-dibromobutan

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 R and S assignments in compounds with two or more stereogenic centers

• When a compound has more than one stereogenic center, the R or S

configuration must be assigned to each of them.

A stereoisomer of 2,3-dibromopenthane Full Name: (2S,3R)-2,3-dibromopenthane

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SUMMARY

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 Fischer Projections

▪ Flat representation of a 3-D 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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Fischer Projections

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 Fischer Rules

• Carbon chain is on the vertical line.

• Highest oxidized carbon is at top.
• Rotation of 180 in plane doesn’t change
molecule.
• Do not rotate 90!

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 90° Rotation

A 90° rotation will change the orientation of the

horizontal and vertical groups.
Do not rotate a Fischer projection 90°.

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 180° Rotation

A rotation of 180° is allowed because it will not

change the configuration.

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 Fischer Mirror Images

Fisher projections are easy to draw and make it easier

to find enantiomers and internal mirror planes when
the molecule has 2 or more chiral centers.

CH 3

H Cl

Cl H

CH 3

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 Fischer (R) and (S)

• Lowest priority (usually H) comes forward, so assignment

rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).
• Example:

CH 3 (S)

H Cl

Cl H

CH 3
(S)

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 Comparing Structures
Are the structures connected the same?

yes no

Are they mirror images? Constitutional Isomers

yes no

Enantiomers
All chiral centers will
Is there a plane of symmetry?
be opposite between them.
yes no

Meso Diastereomers
superimposable

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 In-class problem
1. For each Fischer projection, label each asymmetric carbon as (R) or (S).

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 In-class problem
1. For each Fischer projection, label each asymmetric carbon as (R) or (S).

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 In-class problem: solutions
1. For each Fischer projection, label each asymmetric carbon as (R) or (S).

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 In-class problem
2. Determine the (R) or (S) configuration of each achiral carbon and draw a
Fischer projection.

a) (S)-propane-1,2-diol
d) (R)-butan-2-ol

b) (R)-2-bromobutan-1-ol e) (R)-glyceraldehyde

c) (S)-1,2-dibromobutane

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In-class problem: solutions

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In-class problem: solutions

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 In-class problem
3. Name the following alkanes and label them as (R) or (S)

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 In-class problem: solutions
3. Name the following alkanes and label them as (R) or (S)

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