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Chapter 13 – Stereoisomerism Page 1

Chapter 13 – Stereoisomerism
Topic 20 from the IB HL Chemistry Curriculum

Assessment Statement Obj Teacher’s Notes

20.6.1 Describe stereoisomers as compounds with the 2
same structural formula but with different
arrangements of atoms in space.

20.6.2 Describe and explain geometrical isomerism in 3 Include the prefixes cis- and trans- and the term restricted rotation.
non-cyclic alkenes.

20.6.3 Describe and explain geometrical isomerism in 3 Include the dichloro derivatives of cyclopropane and cyclobutane.
C3 and C4 cycloalkanes.

20.6.4 Explain the difference in the physical and 3 Include cis- and trans-1,2-dichloroethene as examples with different boiling
chemical properties of geometrical isomers. points, and cis- and trans-but-2-ene-1,4-dioic acid as examples that react
differently when heated.

20.6.5 Describe and explain optical isomerism in simple 3 Include examples such as butan-2-ol and 2-bromobutane.
organic molecules. The term asymmetric can be used to describe a carbon atom joined to four
different atoms or groups, and also as a description of the molecule itself.
Include the meanings of the terms enantiomer and racemic mixture.
TOK: The existence of optical isomers provided indirect evidence of a
tetrahedrally bonded carbon atom. This is an example of the power of
reasoning in allowing use access to the molecular scale. Do we know or
believe those carbon atoms are tetrahedrally coordinated? The use of
conventions in representing three-dimensional molecules in two dimensions
could also be discussed.

20.6.6 Outline the use of a polarimeter in 2 Include the meaning of the term plane-polarized light.
distinguishing between optical isomers.

20.6.7 Compare the physical and chemical properties 3

of enantiomers.

Stereoisomerism

The structural isomers discussed in Chapter 03 differ from each other in the order of attachment of the atoms.
Consequently, these are molecules which are fundamentally different from each other, having different amounts of
branching in their chains or different positions of functional groups or even possessing entirely different functional
groups. As we have seen, it is relatively easy to describe the differences between these isomers using structural
formulas in two dimensions.

However, another type of isomerism, known as stereoisomerism, is much harder to describe on paper. This is because
these molecules have atoms attached together in the same order, but differ from each other in their spatial (three-
dimensional) arrangement. You will find that your understanding of this topic will be greatly helped by looking at and
building three-dimensional models of the different molecules. There are two types of stereoisomerism that we will
discuss here, geometric (now more commonly known as cis- trans), and optical isomers.
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Geometric isomers (cis-trans isomers)

When there is some constraint in a molecule that restricts the free rotation of bonded groups, they become fixed in
space relative to each other. So, where there are two different groups attached to each of the two carbon atoms that
have restricted rotation, this gives rise to two different three-dimensional arrangements of the atoms known as
geometric isomers. The restriction on rotation can be caused by a double bond or a cyclic structure as shown below.

Cis- refers to the isomer that has the same groups on the same side of the double bond or ring, while trans- is the isomer
that has the same groups on opposite sides, or across the point of restricted rotation. These prefixes are given in italics
before the name of the compound. Some examples of cis-trans isomerism in these circumstances are discussed below.

Double bond

We learned in Chapter 11 that the double bond consists of one sigma and one pi bond, and that the pi bond forms by
the sideways overlap of two p orbitals. Free rotation around this is not possible as it would push the p orbitals out of
position; and the pi bond would break. For example:
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Molecular graphics of the geometric isomers of 1,2-dibromoethene. The atoms are shown as color-coded cylinders, with carbon in yellow,
hydrogen in white and bromine in red. The cis- form is on the left and the trans- form on the right. The molecule cannot alternate between the
two forms as there is restricted rotation about the carbon-carbon double bond.

Worked example:

Draw and name the geometric isomers of butenedioic acid.

Solution:
As the carboxylic acid groups must be in the terminal positions and cannot be attached to a double bond, the condensed
structural formula must be HOOC-(CH)2-COOH. To identify the geometric isomers, we need to draw this out in full.

Cis- and trans-isomers have different properties depending on the influence of the substituted group in the molecule.

Physical properties
Physical properties depend on:

• the polarity of the molecules

• the shape or symmetry of the molecules.

The polarity strongly influences the relative boiling point as it determines the strength of the intermolecular forces. For
example, cis-1,2-dichloroethene has a net dipole moment and dipole-dipole attractions between its molecules in
addition to the van der Waals' forces, whereas trans-1,2-dichloroethene which is non-polar has only van der Waals'
forces. The boiling point of the cis-isomer is therefore higher.
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Melting point is generally more influenced by the symmetry of the molecules as this affects the packing in the solid
state. The trans-isomers are able to pack more closely due to their greater symmetry, so the intermolecular forces are
more effective than in the cis-isomer. The melting point of the trans-isomer is therefore higher.

A similar comparison is seen with butenedioic acid where the melting point of the trans-isomer is significantly higher
than that of the cis-isomer. Here the cis-isomer is able to form intramolecular hydrogen bonds between the two
-COOH groups due to their close proximity, whereas in the trans-isomer the - COOH groups sticking out on opposite
sides of the molecule are free to form intermolecular hydrogen bonds. Thus more energy is needed to separate the
trans isomer molecules, hence the higher melting point.

Chemical properties
Chemical properties of the cis- and trans- isomers are usually very similar, but an interesting exception to this is seen
with butenedioic acid. Here the two isomers have such different reactivities, as shown by example below in their
responses to being heated, that they were originally given different names.
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The differences in the properties of the cis-and trans- isomers of butenedioic acid become very evident when examples
of their roles in biology are compared. Fumaric acid (trans-) is an intermediate in the Krebs cycle, an essential part of
the reactions of aerobic respiration for energy release in cells. By contrast, maleic acid (cis-) is an inhibitor of reactions
that interconvert amino acids, for example, in the human liver. Their different biological activities are a consequence of
their different shapes affecting their binding to enzymes, the biological catalysts that control all these reactions.
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Cyclic molecules

Cycloalkanes contain a ring of carbon atoms in which the bond angles are strained from the tetrahedral angles in the
parent alkane. For example, in cyclopropane the carbon atoms form a triangle with bond angles of 60°, and in
cyclobutane the atoms form a puckered square with approximate angles of 90°. The ring prevents rotation around the
carbon atoms, so when there are two different groups attached to two carbons in the ring, these molecules can exist as
the cis- and trans- forms. For example:

As you can see from the example of 1,3-dichlorocyclobutane above, the substituted groups do not have to be on
adjacent carbon atoms; it is their position relative to the plane of the ring that defines the geometric isomer.
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Optical isomers

A carbon atom attached to four different atoms or groups is known as asymmetric or chiral. The four groups, arranged
tetrahedrally around the carbon atom with bond angles of 109.5°, can be arranged in two different three-dimensional
configurations which are mirror images of each other. This is known as optical isomerism. The term refers to the ways
in which the isomers interact with plane-polarized light, discussed below. They are said to be chiral molecules and have
no plane of symmetry.

In the following figure, an asymmetric, or chiral, carbon atom, shown in black, is bonded to four different atoms or
groups shown here in different colors. This gives rise to two configurations which are mirror images of each other.

The word chiral is derived from the Greek word for “hand”. Lord Kelvin first introduced the term into science in 1904
with the now celebrated definition: “I call any geometrical figure, or group of points, chiral, and say it has chirality if its
image in a plane mirror, ideally realized, cannot be brought to coincide with itself.” His definition can therefore be
applied much more generally to structures outside
chemistry, such as knots.

If you look at your two hands, you will see that they also are
mirror images. When you put them directly on top of each
other, the fingers and thumbs do not line up - we say they
are non-superimposable.
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The same is true for optical isomers, and the two non-superimposable forms are known as enantiomers. A mixture
containing equal amounts of the two enantiomers is known as a racemic mixture or a racemate. As we will see, such a
mixture is said to be optically inactive.

A single chiral centre in a molecule gives rise to two stereoisomers. ln general, a molecule with n chiral centres has a
maximum of 2n stereoisomers, although some may be too strained to exist. For example, cholesterol has eight chiral
centres and so a possible 28 = 256 stereoisomers. Only one is produced in biological systems.

We can find optical activity in many of the molecules we have already encountered in this chapter. The clue is to look
for any carbon atom that is bonded to four different groups. It is often useful to mark that carbon with an asterisk.

When you are looking for a chiral carbon atom in a molecule, you must look at the whole group bonded to the carbon,
not just the immediately bonded atom – for example CH3 is a different group from C2H5.
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Worked example:

Draw the enantiomers of 2-hydroxypropanoic acid (lactic acid). Mark the chiral carbon atom and show the plane of the
mirror.

Solution

First draw out the full structure and identify the chiral carbon atom.

Properties of optical isomers

Optical isomers, the enantiorners, have identical physical and chemical properties – with two important exceptions:
• optical activity
• reactivity with other chiral molecules

Optical activity
As we know from their name, optical isomers show a difference in a specific interaction with light. A beam of ordinary
light consists of electromagnetic waves that oscillate in an infinite number of planes at right angles to the direction of
travel. If, however, this light is passed through a device called a polarizer, only the light waves oscillating in a single
plane pass through, while light waves in all other planes are blocked out. This is known as plane-polarized light. A
similar effect is achieved in polarized sunglasses or windshields to reduce glare. In the early 1800s, it was discovered
that when a beam of plane-polarized light passes through a solution of optical isomers, they rotate the plane of
polarization.
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The amount and direction of rotation can be measured with an instrument called a polarimeter as shown in the
following figure.

The solution of isomers is placed in the sample tube through which plane polarized light is passed. Rotation of the
polarization plane occurs and the light then passes through a second polarizer called the analyser, which has been
rotated until the light passes through it. Thus the extent and direction of rotation brought about by the sample can be
deduced. In order to compare different solutions, the concentrations of the solutions, the wavelength of light used and
the sample path length must all be kept the same.

The pioneer of polarimetry was Jean Baptiste Biot (1774-1862), a French physicist and older friend of the famous French
bacteriologist Louis Pasteur (1822-1895). Biot showed that some crystals of quartz rotated the plane of polarized light
while other crystals rotated it to the same extent in the opposite direction. Later, by showing the same effect in liquids
such as turpentine, and in solutions of naturally occurring substances such as sugar, he realized it must be a molecular
property and coined the term “optical activity”. In 1848, Pasteur was working on crystalline salts derived from wine and
discovered that while tartaric acid showed optical activity, racemic acid – with the same chemical composition – did not.
He deduced that this was because racemic acid contained an equal mixture of two isomers (such mixtures are now
described as racemic). Pasteur saw the huge significance of this. He reasoned that reactions outside the cell always
produce an optically inactive mixture whereas biological activity is specific to one isomer. In his later work on the origin
of life, this became his guiding distinction between living and inanimate material.

Different notations are used to distinguish the two enantiomers of a pair: (+) and (-) refer to the direction in which the
plane-polarized light is rotated; (+) for a clockwise direction and (-) for anticlockwise rotation. The lower-case letters d-
(dextrorotatory) and 1-(Ievorotatory) respectively have traditionally been used as alternatives for this but are becoming
obsolete. Confusingly, D- and L- are a different, unrelated notation based on spatial configurations in comparison with
the reference molecule glyceraldehyde. This system is widely used in naming many biological molecules such as amino
acids and sugars.

Other molecules are described by their absolute configuration, using R (rectus) for right or clockwise and S (sinister) for
left or counter-clockwise. The rules for determining the absolute configuration are based on atomic number and mass.
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Happily, we will not adopt any particular system here and you will not be expected to identify the specific enantiomer in
any of these examples.

Separate solutions of enantiomers, at the same concentration, rotate plane-polarized light in equal amounts but
opposite directions. A racemic mixture does not rotate the light, which is why it is said to be optically inactive. Naturally
occurring chiral molecules are optically active, in other words they exist as only one enantiomer. For example, morphine
rotates plane-polarized light to the left so is said to be (- ), whereas sucrose rotates plane-polarized light to the right and
is said to be (+).

Reactivity with other chiral molecules

When a racemic mixture is reacted with a single enantiomer of another chiral compound, the two components of the
mixture, the (+) and ( - ) enantiomers, react to produce different products. These products have distinct chemical and
physical properties and so can be separated from each other relatively easily. This method of separating the two
enantiomers from a racemic mixture is known as resolution. The different reactivity of a pair of enantiomers with
another chiral molecule is of particular significance in biological systems because these are chiral environments. An
infamous example of the different reactivities of enantiomers occurred in the 1960s when thalidomide was prescribed
to pregnant women for morning sickness. One enantiomer is therapeutic but the other produces severe malformations
in the fetus. This tragedy largely spearheaded research into processes for the manufacture of a single enantiomer using
a chiral catalyst. The process, known as asymmetric synthesis, was developed by three scientists who shared the Nobel
Prize in Chemistry in 2001.

Other examples of the importance of chirality from biology include the fact that taste buds on the tongue and sense
receptors in the nose contain chiral molecules and so interact differently with the different enantiomers. For example,
D-amino acids all taste sweet, whereas L-amino acids are often tasteless or bitter. Similarly, we can distinguish between
the smells of oranges and lemons due to the presence of different enantiomers of the compound limonene.
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Problems: Answer each problem. For multiple choice questions, include your reasoning in the margins.

Which compound can exist as optical isomers?

A. CH3CHBrCH3
B. CH2ClCH(OH)CH2CI
C. CH3CHBrCOOH
D. CH3CCI2CHOH

Write the structure of the first alkane in the homologous series to show optical isomerism.

Draw and name the geometric isomers of:

(a) pent-2-ene

(b) 2,3-dichlorobut-2-ene.

Which species will show optical activity?

A. 1-chloropentane
B. 3-chloropentane
C. 1-chloro-2-methylpentane
D. 2-chloro-2-methylpentane
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(a) (i) The compound C3H6 can react with bromine. Write an equation for this reaction and name the product.
State a visible change which accompanies the reaction. (3)

(ii) Give the full structural formula of the product formed in part (a)(i), and identify, by using an asterisk (*), a
chiral carbon atom. State what distinctive property a chiral carbon atom gives to a molecule. (2)
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(This question is continued on the next page.)

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