CHAPTER THREE

STEREOCHEMISTRY

1
Definitions
• Stereochemistry is the study of three-dimensional
arrangements of atoms in molecules.
• The Greek word stereos means “solid,” and stereochemistry
refers to chemistry in three dimensions.
• Isomers are compounds that have the same numbers and the
same kinds of atoms, but they differ in the way their atoms
are arranged.
Classes of Isomers
 Constitutional isomer
 Stereoisomer
 Conformational isomer

2
i. Constitutional isomers differ in the way their atoms are
connected.

Example of constitutional isomers

Cl

CH3CH2OH and CH3OCH3 CH3CH2CH2CH2Cl and CH3CH2CHCH3

ethanol dimethyl ether 1-chlorobutane 2-chlorobutane

O
O
CH3CH2CH2CH2CH3 and CH3CHCH2CH3 CH3CCH3 and CH3CH2CH
propan-2-one propionaldehyde
pentane CH3
2-methylbutane

3
ii. Stereoisomers (Configurational isomers)
• Unlike the atoms in constitutional isomers, the atoms in
stereoisomers are connected in the same way.
• Stereoisomers differ in the way their atoms are arranged
in space.
• They are different compounds that do not readily
interconvert.
• Therefore, they can be separated. There are two kinds of
stereoisomers: cis–trans isomers and optical isomers.

4
Cis–Trans Isomers
• Cis–trans isomers (also called geometric isomers) result from
restricted rotation.
• Restricted rotation can be caused either by a double bond or by a
cyclic structure.
• As a result of the restricted rotation about a carbon–carbon double
bond, an alkene such as 2-pentene can exist as cis and trans
isomers.
• The cis isomer has the hydrogens on the same side of the double
bond, whereas the trans isomer has the hydrogens on opposite sides
of the double bond.

H2C CH3
H3C H2C CH3 H

H
H H H3C
cis-2-pentene trans-2-pentene 5
Cyclic compounds can also have cis and trans isomers.
The cis isomer has the hydrogens on the same side of the ring,
whereas the trans isomer has the hydrogens on opposite sides of the
ring.
H H

Br Cl
Br Cl

cis-1-bromo-3-chlorocyclobutane trans-1-bromo-3-chlorocyclobutane

Optical isomers
Optical isomers are configurational isomers which are able to rotate
plane-polarised light clockwise or anticlockwise.
iii. Conformational isomers are different shapes of the same
molecule resulting from rotation around a single C-C bond.
They are not different compounds (i.e. they have the same physical
and chemical properties) and are readily interconvertible. 6
 Chirality
 An object with a right-handed and a left-handed form is said
to be chiral.
 Notice that chirality is a property of an entire object.
 A chiral object has a nonsuperimposable mirror image.
 In other words, its mirror image is not the same as itself.
 Similarly, a molecule is chiral if its two mirror-image forms are
not superposable in three dimensions.
 A hand is chiral because if you look at your left hand in a
mirror, you do not see your left hand; you see your right
hand.
 In contrast, a chair is not chiral it looks the same in the mirror.
Objects that are not chiral are said to be achiral.

7
 A molecule is not chiral if it has a plane of symmetry.
 A plane of symmetry is a plane that cuts through the middle
of a molecule (or any object) in such a way that one half of
the molecule or object is a mirror image of the other half.
 An achiral object has a superimposable mirror image.
 Some other achiral objects would be a table, a fork, and a
glass.

8
 A molecule that has a plane of symmetry in any
conformation must be identical to its mirror image and hence
must be nonchiral, or achiral.
 Thus, propanoic acid, CH3CH2CO2H, has a plane of symmetry
and is achiral, while lactic acid, CH3CH(OH)CO2H, has no
plane of symmetry in any conformation and is chiral.

9
• The feature that most often cause of chirality in a molecule is
an asymmetric carbon.
• An asymmetric carbon is a carbon atom that is bonded to
four different groups.
• For example, the starred carbon in 4-octanol is an asymmetric
carbon because it is bonded to four different groups (H, OH,
CH2CH2CH3 and CH2CH2CH2CH3).
• The starred carbon in 2,4-dimethylhexane is an asymmetric
carbon because it is bonded to four different groups: methyl,
ethyl, isobutyl, and hydrogen.

Br
OH *
*
*
4-octanol 2-bromobutane 2,4-dimethylhexane 10
• Notice that the only carbons that can be asymmetric carbons
are sp3 hybridized carbons; sp2 and sp hybridized carbons
cannot be asymmetric carbons because they cannot have four
groups attached to them.
• An asymmetric carbon is also known as a chirality center or
stereogenic center.
• Atoms other than carbon, such as nitrogen and phosphorus,
can be chirality centers when they are bonded to four
different atoms or groups.

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 Isomers with One Asymmetric Carbon
• A compound with one asymmetric carbon, such as 2-bromobutane,
can exist as two different stereoisomers.
• The two isomers are analogous to a left and a right hand.
• Imagine a mirror between the two isomers; notice how they are
mirror images of each other.
• The two stereoisomers are nonsuperimposable mirror images and
they are different molecules.
CH3CHCH2CH3

Br
2-bromobutane

Br Br

C C
H H
H3CH2C CH2CH3
CH3 H3C

12
mirror
• Nonsuperimposable mirror-image molecules are called
enantiomers.
• The two stereoisomers of 2-bromobutane are enantiomers.
• A molecule that has a nonsuperimposable mirror image, like
an object that has a nonsuperimposable mirror image, is
chiral.
• Each of the enantiomers is chiral.
• A molecule that has a superimposable mirror image, like an
object that has a superimposable mirror image, is achiral.
• To see that the achiral molecule is superimposable on its
mirror image (i.e., they are identical molecules), mentally
rotate the achiral molecule clockwise.

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 Br Br Br Br
C C C C
H H CH3 CH2CH3
H3CH2C H 3C CH2CH3 H3CH2C H3C
CH3 CH3
H3C
chiral achiral molecule supperimposable
molecule nonsuperimposable
mirror image mirror image
enantiomers identical molecule

Enantiomers share many of the same properties.

They have the same boiling points, the same melting points,
and the same solubilities.
a) One of the properties that enantiomers do not share is
the way they interact with polarized light.
b) And they react in different way with other chiral
molecule.

14
 Properties of Chiral Molecules: Optical Activity
• Optical activity is the ability of a chiral substance to rotate the
plane of plane-polarized light.
• Normal light consists of electromagnetic waves that oscillate in all
directions.
• Plane-polarized light (or simply polarized light), in contrast,
oscillates only in a single plane passing through the path of
propagation. Polarized light is produced by passing normal light
through a polarizer such as a polarized lens or a Nicol prism.

15
When polarized light passes through a solution of achiral molecules,
the light emerges from the solution with its plane of polarization
unchanged.
An achiral compound does not rotate the plane of polarization.
It is optically inactive.

16
• However, when polarized light passes through a solution of chiral
compound, the light emerges with its plane of polarization
changed.
• Thus, chiral compound rotates the plane of polarization.
• Chiral compound will rotate the plane of polarization clockwise or
counterclockwise.
• If one enantiomer rotates the plane of polarization clockwise, its
mirror image will rotate the plane of polarization exactly the same
amount counterclockwise.

17
• A compound that rotates the plane of polarization is said to be
optically active.
• In other words, chiral compounds are optically active and
achiral compounds are optically inactive.
• If an optically active compound rotates the plane of
polarization clockwise, it is called dextrorotatory, indicated by
(+).
• If an optically active compound rotates the plane of
polarization counterclockwise, it is called levorotatory,
indicated by (-).
• Sometimes lowercase d and l are used instead of (+) and (-).
• The device that is used for measuring the effect of optically
active compounds on plane-polarized light is a polarimeter.

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• A solution containing equal quantities of enantiomers
therefore exhibits no net rotation.
• Enantiomeric forms of a chiral molecule cause a rotation of
the plane of polarization in exactly equal amounts but in
opposite directions.
• Mixtures containing equal quantities of enantiomers are
called racemic mixtures.
• Racemic mixtures are optically inactive. A mixture of equal
amounts of two enantiomers such as (R)-(-) lactic acid and (S)-
(+) -lactic acid is called a racemic mixture or a racemate.
• The symbol (±) is used to specify a racemic mixture. Thus, (±)-
2-bromobutane indicates a mixture of (+)-2-bromobutane
and an equal amount of (-)-2-bromobutane.

19
• Conversely, when one enantiomer is present in excess, a net rotation of
the plane of polarization is observed.
• At the limit, where all the molecules are of the same handedness, we say
the substance is optically pure.
• Optical purity, or percent enantiomeric excess, is defined as:
Optical purity = percent enantiomeric excess
= percent of one enantiomer - percent of other
enantiomer
Specific Rotation
The number of degrees that the plane of polarization is rotated as the light
passes through a solution of an enantiomer depends on the number of
chiral molecules that it encounters.
specific rotation, [α]

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 Configuration of Chiral Compounds: The Cahn-Ingold-Prelog (CIP)
Sequence Rules for Assigning Configurations
• We need a way to name the individual stereoisomers of a
compound such as 2-bromobutane so that we know which
stereoisomer we are talking about.
• In other words, we need a system of nomenclature that indicates
the configuration (arrangement) of the atoms or groups about the
asymmetric carbon.
• 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.

21
• Let’s first look at how we can determine the configuration of a
compound if we have a three-dimensional model of the compound.

• Rule 1. Look at the four atoms directly attached to the chirality

center, and rank them according to atomic number. The atom with
the highest atomic number has the highest ranking (first), and the
atom with the lowest atomic number (usually hydrogen) has the
lowest ranking (fourth). When different isotopes of the same
element are compared, such as deuterium (2H) and protium (1H),
the heavier isotope ranks higher than the lighter isotope.
• Thus, atoms found in bromochlorofluoromethane have the
following order.
22
 3 4
H this has the lowest priority (least ranked)
F
1
C Br
this has the highest priority
2 Cl

• Rule 2. If a decision can’t be reached by ranking the first atoms in

the substituent, look at the second, third, or fourth atoms away
from the chirality center until the first difference is found.
• A -CH2CH3 substituent and a -CH3 substituent are equivalent by
rule 1 because both have carbon as the first atom. By rule 2,
however, ethyl ranks higher than methyl because ethyl has a
carbon as its highest second atom, while methyl has only hydrogen
as its second atom. Look at the following pairs of examples to see
how the rule works:
23
24
Rule 3. Multiple-bonded atoms are equivalent to the same number
of single bonded atoms. For example, an aldehyde substituent
(=CHO), which has a carbon atom doubly bonded to one oxygen, is
equivalent to a substituent having a carbon atom singly bonded to
two oxygens:

25
• Having ranked the four groups attached to a chiral carbon, we
describe the stereochemical configuration around the carbon by
orienting the molecule so that the group with the lowest ranking (4)
points 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.
• If a curved arrow drawn from the highest to second-highest to third-
highest ranked substituent (1 → 2 → 3) is clockwise, we say that the
chirality center has the R configuration (Latin rectus, meaning
“right”).
• If an arrow from 1 → 2→ 3 is counterclockwise, the chirality center
has the S configuration (Latin sinister, meaning “left”).
26
• Look at (2)-lactic acid for an example of how to assign configuration.
• Sequence rule 1 says that -OH is ranked 1 and -H is ranked 4, but it
doesn’t allow us to distinguish between -CH3 and -CO2H because both
groups have carbon as their first atom.
• Sequence rule 2, however, says that -CO2H ranks higher than -CH3
because O (the highest second atom in -CO2H) outranks H (the highest
second atom in -CH3).
• Now, turn the molecule so that the fourth-ranked group (-H) is oriented
toward the rear, away from the observer. Since a curved arrow from 1 (-
OH) to 2 (-CO2H) to 3 (-CH3) is clockwise (right turn of the steering
wheel), (2)-lactic acid has the R configuration.

1 2 2
H 1
HO H CO2H HO2C OH
C C
CH3 CH3
3 3
R configuration S configuration
(-)-Lactic acid (+)-Lactic acid 27
Example, we will determine which of the enantiomers of 2-
bromobutane has the R configuration and which has the S
configuration.

1 1
Br Br
4
C 4 H C
H CH2CH3
H3CH2C CH3 H 3C
2 2
3 3

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).
If the arrow points clockwise, the compound has the R configuration,
and if it points counterclockwise, the compound has the S
configuration.
28
 1 1
Br Br
4
C 4 H C
H CH2CH3
H3CH2C CH3 H3C
2 2
3 3
(S)-2-bromobutane (R)-2-bromobutane

• Compounds in which a stereogenic center is part of a ring are handled

in an analogous fashion. To determine, for example, whether the
configuration of (+)-4-methylcyclohexene is R or S, treat the right- and
left-hand paths around the ring as if they were independent
substituents.

The absolute configuration is R. 29

 Fischer Projections
 Stereochemistry deals with the three-dimensional
arrangement of a molecule’s atoms, and we have attempted
to show stereochemistry with wedge-and-dash drawings and
computer-generated models.
 It is possible, however, to convey stereochemical information
in an abbreviated form using a method devised by the German
chemist Emil Fischer.
 Molecules with asymmetric carbons can be represented by
Fischer projections, in which a tetrahedral carbon atom is
represented by two crossed lines.
 The vertical lines represent the bonds pointing into the page
(away from the reader), and the horizontal lines represent the
bonds pointing out of the page (towards the reader).

30
 Let’s return to bromochlorofluoromethane as a simple example of a
chiral molecule.
 Fischer projections are always generated the same way: the molecule is
oriented so that the vertical bonds at the stereogenic center are
directed away from you and the horizontal bonds point toward you.
 A projection of the bonds onto the page is a cross. The stereogenic
carbon lies at the center of the cross but is not explicitly shown.

31
 It is customary to orient the molecule so that the carbon
chain is vertical with the lowest numbered carbon at the top
as shown for the Fischer projection of (R)-2-butanol.
 The compound is usually drawn so that the main carbon
skeleton is vertical and the highest priority functional group is
at the top of the vertical line.

CH3 CH3

HO C H corresponds to OH H

CH2CH3 CH2CH3
(R)-2-butanol

32
 Configuration of a compound drawn as a Fischer projection
 Rank the groups (or atoms) that are bonded to the asymmetric
carbon in order of priority.
 Draw an arrow from the group (or atom) 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; if it points counterclockwise; the enantiomer has
the S configuration, provided that the group with the lowest
priority (4) is on a vertical bond.
1
1
Cl Cl

CH3CH2 CH2CH2CH3 H3CH2CH2C CH2CH3

3 2 2 3
H4 H4
(R)-3-Chlorohexane (S)-3-chlorohexane 33
 If the group (or atom) with the lowest priority is on a horizontal
bond, the answer you get from the direction of the arrow will be
the opposite of the correct answer.
 For example, if the arrow points clockwise, suggesting that the
asymmetric carbon has the R configuration, it actually has the S
configuration; if the arrow points counterclockwise, suggesting
that the asymmetric carbon has the S configuration; it actually
has the R configuration.
 In the following example, the group with the lowest priority is on
a horizontal bond, so clockwise signifies the S configuration, not
the R configuration.
3 3
CH3 CH3
1 1 4
4 HO C H
H OH
CH2CH3
CH2CH3 2
2 (R)-2-butanol
(S)-2-butanol 34
• In drawing the arrow from group 1 to group 2, you can draw
past the group (or atom) with the lowest priority (4), but
never draw past the group (or atom) with the next lowest
priority (3).
O O
2
COH 2 COH
3 3 4
4H CH3 H3C H

1OH 1 OH
(S)-lactic acid (R)-lactic acid

It is easy to tell whether two molecules are enantiomers

(nonsuperimposable) or identical molecules (superimposable) if you have
molecular models of the molecules just see whether the models
superimpose. If one has the R configuration and the other has the S
configuration, they are enantiomers. If they both have the R configuration
or both have the S configuration, they are identical molecules. 35
 Multiple Stereogenic Centers
 Many organic compounds have more than one asymmetric
carbon.
 The more asymmetric carbons a compound has, the more
stereoisomers are possible for the compound.
 If we know how many asymmetric carbons a compound has,
we can calculate the maximum number of stereoisomers for
that compound: a compound can have amaximum of
𝟐𝒏 stereoisomers(provided it doesn’t have any other
stereocenters), where n equals the number of asymmetric
carbons and the number of pairs of enantiomers will be 2n-1.
 For example, 3-chloro-2-butanol has two asymmetric
carbons. Therefore, it can have as many as four
stereoisomers. The four stereoisomers are shown both as
perspective formulas and as Fischer projections. 36
 * *
CH3CHCHCH3

Cl OH
3-chloro-2-butanol
Cl Cl
H CH3 H3 C H
C1 1C
1) 2)
enantiomers
C2 C2
H
H 3C H CH3
OH OH
diastereo 1S,2R
1R,2S mers

H H
H3 C Cl
Cl CH3
C1 1C
3) 4)
enantiomers 2
C2 C
CH3
H3C H
H OH
OH
1S,2S 1R,2R 37
 The four stereoisomers of 3-chloro-2-butanol consist of two
pairs of enantiomers.
 Stereoisomers 1 and 2 are nonsuperimposable mirror images.
 Therefore, they are enantiomers. Stereoisomers 3 and 4 are
also enantiomers.
 Stereoisomers 1 and 3 are not identical, and they are not
mirror images.
 Such stereoisomers are called diastereomers.
 Diastereomers: are stereoisomers that are not enantiomers.
 Diastereoisomers (or diastereomers) are stereoisomers that
are not mirror images of each other.
 Numbers 1 and 4, 2 and 3, and 2 and 4 are also
diastereomers.

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 Enantiomers have identical physical properties (except for the
way they interact with polarized light) and identical chemical
properties they react at the same rate with a given achiral
reagent.
 Diastereomers have different physical properties (different
melting points, different boiling points, different solubilities,
different specific rotations, and so on) and different chemical
properties they react with the same achiral reagent at
different rates.
 Note carefully the difference between enantiomers and
diastereomers: enantiomers have opposite configurations at
all chirality centers, whereas diastereomers have opposite
configurations at some (one or more) chirality centers but the
same configuration at others.
39
 Meso Compounds
• In the examples we have just seen, each compound with two
asymmetric carbons has four stereoisomers.
• However, some compounds with two asymmetric carbons
have only three stereoisomers. An example
CH3CHCHCH3

Br Br
2,3-dibromobutane

CH3
H3 C Br H3 C H H
C C H C C Br C C
H H Br H
Br CH3 Br CH3 H3 C Br
1 2 3
stereoisomers of 2,3-dibromobutane

40
• The “missing” isomer is the mirror image of 1 because 1 and
its mirror image are the same molecule. This can be seen
more clearly if you look either at the perspective formulas
drawn in their eclisped conformations or at the Fischer
projections. CH CHCHCH 3 3

Br Br
2,3-dibromobutane

CH3 CH3 H 3C CH3

H 3C H 3C
C C H C C Br C C
H H Br H
Br Br Br H H Br
1 2 3
stereoisomers of 2,3-dibromobutane

It is obvious that 1 and its mirror image are identical when

looking at the perspective formula in the eclipsed
conformation. 41
 • To convince yourself that the Fischer projection of 1 and its
mirror image are identical, rotate the mirror image by 180°.
(Remember, you can move Fischer projections only by rotating
them 180° in the plane of the paper.)
CH3 CH3
CH3 CH3
H3 C H3 C H Br Br H
C C H C C H
H H H Br Br H
Br Br Br Br
1 2 CH3 CH3
superimposable superimposable
mirror image mirror image

 Stereoisomer 1 is called a meso compound. Even though a meso

compound has asymmetric carbons, it is an achiral molecule
because it is super imposable on its mirror image.
 Mesos is the Greek word for “middle.”
 A meso compound is achiral; when polarized light is passed
through a solution of a meso compound; the plane of polarization
is not rotated. 42
 A meso compound can be recognized by the fact that it has
two or more asymmetric carbons and a plane of symmetry.
 If a compound has a plane of symmetry, it will not be optically
active even though it has asymmetric carbons.
 A plane of symmetry cuts the molecule in half, and one half is
the mirror image of the other half.
 Stereoisomer 1 has a plane of symmetry, which means that it
does not have a nonsuperimposable mirror image it does not
have an enantiomer.

43
 It is easy to recognize when a compound with two asymmetric
carbons has a stereoisomer that is a meso compound the four
atoms or groups bonded to one asymmetric carbon are
identical to the four atoms or groups bonded to the other
asymmetric carbon.
 A compound with the same four atoms or groups bonded to
two different asymmetric carbons will have three
stereoisomers: One will be a meso compound, and the other
two will be enantiomers.

H3C OH H3C CH3

H H
C C H C C OH C C
H H HO H
HO CH3 HO CH3 H3C OH

meso compound enantiomers

44
 Diastereoisomers versus Enantiomers
 Enantiomers have identical chemical and physical
properties, except for their biological activity (i.e. they
interact differently with other chiral molecules) and their
effects on plane-polarised light.
 Diastereoisomers can have different physical
(e.g. melting point, polarity) and chemical properties.
 Enantiomers are always chiral.
 Diastereoisomers can be chiral or achiral.

45
 Resolution of Racemic Mixtures
 Resolution: “Separation of enantiomers from either racemic
mixture of enantiomerically enriched mixture.”
 Resolution is necessary to prepare optically pure chiral auxiliaries,
to purify products of low enantiomeric excess and it is valid strategy
for chiral synthesis.
 Enantiomers can be resolved chemically or chromatographically.
1) Resolution Through Formation Of Diastereomers
(Chemical Method)
 Pasteur developed method for formation of diastereomeric salts &
their fractional crystallisation is best method of resolution.
 To separate a racemic mixture, we first react with a chiral reagent.
 The product will be a pair of diastereomers.
 These, differ in all types of physical properties and can therefore be
separated by ordinary methods.
46
 • Example

Racemic mixture
47
 The Chirality of Biomolecules
• Thalidomide is teratogenic (causes birth defects).
• It is estimated that more than 10,000 children
worldwide were born with deformed or missing
limbs.
• Thalidomide is chiral and was sold as a racemic
mixture of its two enantiomers.

• The enantiomer on the left (R) is primarily

responsible for reducing nausea, whereas the one
on the right (S) is responsible for the teratogenic
properties. 48
 Chiral Compounds Without Chiral Atoms

There are some molecules that do not contain chiral

carbons but are chiral.
• Biphenyls: some ortho substituted biphenyls are
locked into one of two chiral, enantiomeric
staggered conformations.

49
Allenes: Compounds containing a C=C=C unit are called allenes.
In allene, the central C atom is sp hybridized, but the two outer
carbons are sp2. The whole molecule does not lie in the same
plane.
An allene is chiral if each end has two distinct
substituents.

H H
H H
C C C C C C
Cl Cl
CH3 CH3

Enantiomers of 2,3-pentadiene 50
 Conformational Isomers
 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.
 Any three-dimensional arrangement of atoms that results
from rotation about single bonds is called a conformation.
 Compounds are three dimensional, but we are limited to a
two-dimensional sheet of paper when we show their
structures.
 Perspective formulas, sawhorse projections, and Newman
projections are methods chemists commonly use to represent
on paper the three-dimensional spatial arrangements of the
atoms that result from rotation about a bond.

51
 In a Newman projection, you are looking down the length of
a particular carbon–carbon bond.
 The carbon in front is represented by the point at which three
bonds intersect, and the carbon in back is represented by a
circle.
 Different conformations are often called conformational
isomers or conformers.
Ethane Conformation: it has two conformers. These are;
i) staggered conformation
ii) eclipsed conformation

52
53
 In staggered conformation of ethane, the three C-H bonds on
one carbon are as far apart as possible from those bonds on
the adjacent carbon.
 The three atoms or groups of atoms on the carbon nearer
your eye are shown on lines extending from the center of the
circle at angles of 120°.

 The three atoms or groups of atoms on the carbon farther

from your eye are shown on lines extending from the
circumference of the circle, also at angles of 120°. 54
• The above figure shows a ball-and-stick model and a 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.
• In other words, hydrogen atoms on the back carbon are
eclipsed by the hydrogen atoms on the front.

55
• In principle, there are an infinite number of conformations of
ethane that differ only in the degree of rotation about the
carbon-carbon single bond.
• Because there is a small energy barrier between
conformations, rotation is not completely free.
• As we shall see, the lowest energy (the most stable)
conformation of ethane is a staggered conformation. The
highest energy (the least stable) conformation is an eclipsed
conformation.
• At room temperature, ethane molecules undergo collisions
with sufficient energy so that the energy barrier between
extreme conformations can be crossed and rotation about the
carbon-carbon single bond from one conformation to another
occurs rapidly.

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 Conformation of Butane
• The conformations of butane viewed along the bond between
carbons 2 and 3.
• For butane, there are two types of staggered conformations
and two types of eclipsed conformations.
• The staggered conformation in which the methyl groups are
the maximum distance apart (θ=180°) is called the anti
conformation; the staggered conformation in which they are
closer together (θ=60°) is called the gauche conformation.
• In one eclipsed conformation (θ=0°), methyl is eclipsed by
methyl.
• In the other (θ= 120°), methyl is eclipsed by hydrogen.

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• Anti conformation: A conformation about a single bond in
which two groups on adjacent carbons lie at a dihedral angle
of 180°.
• Gauche conformation: A conformation about a single bond of
an alkane in which two groups on adjacent carbons lie at a
dihedral angle of 60°.
• Note that both the gauche and anti conformations of butane
are staggered conformations, yet the gauche conformations
are higher in energy than the anti conformation.
• The lowest energy conformation occurs when the two methyl
groups are the maximum distance apart (𝜃=180°).
• The highest energy conformation occurs when the two
methyl groups are eclipsed (𝜃= 0°).
• In dealing with the relative stabilities of the various
conformations of butane, we again encounter torsional strain.

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Eclipsed conformation of butane Guache conformation of butane

• The most stable conformation for a straight-chain alkane is a

zigzag shape, as the alkyl groups are as far apart as possible.
• (This is why we draw alkyl chains with a zigzag structure.)

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 Conformations of cycloalkanes
• The shape of cycloalkanes is determined by torsional strain, steric strain
and angle strain.
• Angle strain. For an sp3 hybridised carbon atom, the ideal bond angle is
109.5° (tetrahedral).
• Angle strain is the extra energy that a compound has because of non-
ideal bond angles (i.e. angles above or below 109.5°).
• Cyclopentane (5-membered) and cyclohexane (6-membered) rings are
therefore the most stable and, consequently, the most easily formed.
Cycloalkanes can adopt different conformations (or shapes):
cyclopropane is flat, cyclobutane can form a butterfly shape,while
cyclopentane can form an open-envelopeshape.

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 Cyclopentane
• If cyclopentane were to adopt a planar conformation, all C-C-
C bond angles would be 108°.
• This angle differs only slightly from the tetrahedral angle of
109.5°; consequently, there would be little angle strain in this
conformation.
• In a planar conformation, however, there are 10 pairs of fully
eclipsed C-H bonds creating a torsional strain.
• To relieve at least a part of this torsional strain, the ring
twists by rotations along the C-C bonds into the “envelope”
conformation.
• In this conformation, four carbon atoms are in a plane, and
the fifth bends out of the plane, rather like an envelope with
its flap bent upward.
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 Cyclohexane
• Cyclohexane adopts the chair or boat conformations, which
are both free of angle strain.
• However, the boat conformation is less stable because of
steric strain between the C-1 and C-4 (or flagstaff ) hydrogens.
• The two chair forms can interconvert via the boat form in a
process known as ring-flipping.

Conformations of cyclohexane
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 Conformations of Mono-substituted Cyclo-hexanes
 Unlike cyclohexane, which has two equivalent chair
conformers, the two chair conformers of a mono substituted
cyclohexane such as methyl cyclohexane are not equivalent.
 The chair conformer with the methyl substituent in an
equatorial position is the more stable conformer because a
substituent has more room and, therefore, fewer steric
interactions when it is in an equatorial position.
 When the methyl group is in an equatorial position, it is anti to
the C-3 and C-5 carbons.
 Therefore, the substituent extends into space, away from the
rest of the molecule.
 In contrast, when the methyl group is in an axial position, it is
gauche to the C-3 and C-5 carbons.
 As a result, there are unfavorable steric interactions between
the axial methyl group and both the axial substituent on C-3
and the axial substituent on C-5 (in this case, hydrogens).

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• Because the interacting substituents are on 1,3-positions
relative to each other, these unfavorable steric interactions
are called 1,3-diaxial interactions.

An equatorial substituent on the C-1 carbon is anti to the C-3 and C-5 carbons.

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An axial substituent on the C-1 carbon is gauche to the C-3 and C-5 carbons.

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 Conformations of Di-substituted Cyclo-hexanes
• Let’s start by looking at 1,4-dimethylcyclohexane.
• First of all, note that there are two different
dimethylcyclohexanes.
• One has both methyl substituents on the same side of the
cyclohexane ring; it is called the cis isomer.
• The other has the two methyl substituents on opposite sides of
the ring; it is called the trans isomer.
• Cis-1,4-Dimethylcyclohexane and trans-1,4-dimethylcyclohexane
are called geometric isomers or cis–trans isomers:

H CH3

CH3 H
H H3C

CH3 H

cis-1,4-dimethyl cyclohexane trans-1,4-dimethylcyclohexane 66

• A general way to recognize a trans disubstituted cyclohexane is to notice
that one group is attached by the upper bond (of the two to its carbon)
and one by the lower bond:

• In a cis 1,4-disubstituted cyclohexane both groups are attached by an

upper bond or both by a lower bond. For example,

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• First we will determine which of the two chair conformers of cis-
1,4-dimethylcyclohexane is more stable.
• One chair conformer has one methyl group in an equatorial
position and one methyl group in an axial position.
• The other chair conformer also has one methyl group in an
equatorial position and one methyl group in an axial position.
• Therefore, both chair conformers are equally stable.

H equatorial
H
CH3 ring flip
H3C
H H
CH3 CH3
axial

cis-1,4-dimethyl cyclohexane
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• In contrast, the two chair conformers of trans-1,4-
dimethylcyclohexane have different stabilities because one has
both methyl substituents in equatorial positions and the other
has both methyl groups in axial positions.
equatorial axial
H
CH3
CH3 ring flip
H
H3C H

equatorial H CH3
axial

trans-1,4-dimethyl cyclohexane

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• The chair conformer with both substituents in axial positions has
four 1,3-diaxial interactions, causing it to be about
4×0.9Kcal/mol=3.6Kcal.mol (15.1 kJ mol) less stable than the
chair conformer with both methyl groups in equatorial positions.
• We can, therefore, predict that trans-1,4-dimethylcyclohexane
will exist almost entirely in the more stable equatorial
conformation.

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