STEREOCHEMISTRY
AN EXERCISE WITH MOLECULAR MODELS
Objective: To learn about the three-dimensional aspects of chemical structures
and isomerism by using molecular models.
Stereochemistry is a very important and reasonably subtle structural aspect of
organic chemistry. Stereoisomers are isomers that have the same general connectivity but
different configurations. Consider the two stereoisomeric forms of lactic acid shown here.
We see that they have the same general connectivity; that is, there are three connected
carbon atoms: one carbon is part of a carboxyl group; the next bears an H and an OH; and
the third, three hydrogens.
HO
CH3
H
H
C
C
COOH
(+)-Lactic acid
HOOC
mirror plane
OH
CH3
(-)-Lactic acid
Careful scrutiny, however, shows that the structures of these two compounds are not
the same. If (-)-Lactic acid were rotated 180o, it would not be superimposable on (+)Lactic acid, which would be the case if they were identical. This is a characteristic of a
molecule that does NOT have a plane of symmetry. A plane of symmetry is an
imaginary plane that divides an object or molecule into two equal halves that are mirror
image reflections of each other. If an imaginary plane were placed so as to include H-CCOOH in (+)-Lactic acid, for example, then the CH3- on one side would not be the same
as the -OH on the other. Lactic acid is said to be chiral since the two forms are related
to each other like the left and right hands, Your left hand does not have a plane that
divides it into two identical mirror image halves. Your left hand is therefore chiral.
Because your left hand is chiral, it will not fit into a right-handed glove. An object or
molecule that has a plane of symmetry is superimposable on its mirror image and is
achiral. A ball, for example, has a plane of symmetry that cuts the ball in half: one side
of the plane, the half-sphere is the exact mirror reflection of the half sphere on the other
side of the plane. The ball is therefore achiral.
The easiest way to detect a chiral molecule is to look for a plane of symmetry. If the
molecule does not have a plane of symmetry, then it is chiral, and its mirror image will not
be superimposable. Since the chiral molecule and its mirror image are not superimposable,
they are not the same compound. The nonsuperimposable mirror images are known as
enantiomers. A necessary condition for not having a plane of symmetry around a
tetrahedral carbon is to have four different substituents (ligands). The carbon atom is a
chiral carbon, a stereocenter, stereogenic center, or a chiral center (these words are
used interchangeably). Molecules with ONE stereocenter do not have a plane of symmetry
and are chiral. With MORE THAN ONE stereocenter, they can be chiral or achiral, because
molecules with more than one stereocenter can have a plane of symmetry. So the most
important way to detect a chiral molecule is to look for a plane of symmetry.
In Fig. 1 we see another pair of enantiomers, and we find that
structure II does not produce structure I. These enantiomers are
possible because again there is no plane of symmetry when there is
attempts to rotate
because again there
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is no plane of symmetry when there is one stereocenter (four different groups are attached
to the central sp3 carbon), a fact that is true for both lactic acid (H, OH, CH3, and COOH)
and for the trihalo compound (H, F, Cl, Br)
Enantiomer pair
H
H
C
Cl
Br
F
I
Br C Cl
F
II
mirror plane
Br
F
H
H
C
C
Cl
II
Rotate about C-H bond
Cl
F
Br
Remains as a nonsuperimposable
mirror image to I.
Enatiomeric to I.
Figure 1. Stereoisomers: Enantiomers
When we look at a compound in which two of the substituents on the central carbon are
identical (bromine, Figure 2a), we no longer have a chiral center. The fundamental
property of these achiral molecules is a plane of symmetry. The consequence of this
is made clear in Figure 2a when we rotate the second of the representations of the mirrorrelated pair. We find that this second structure is identical to the first, because it is
superimposable on the first. Thus, this dibromo compound is achiral.
Identical pair
(a)
C
Br C
Cl
Br
I'
H
H
H
Cl
Mirror plane
H
C Br
Cl
Br
II'
Br
Br
C
Cl
H
Br
Br
II'
Rotate about C-H bond
Br C
Cl
Br
Identical to I'
H
Br C Br
Cl
Plane of symmetry
Figure 2a Achiral structures: Internal mirror planes in dibromochloromethane
2
H
(b)
H3C
C C
H
H
CH3
CH3
C=C
H
CH3
Figure 2b. Achiral structures: Internal mirror planes in cis-2-butene.
The question now arises, How do we know when a compound is chiral; that is, what
analysis can be done to detect chirality? And how can we separate the pair and tell which is
which? A pair of enantiomeric compounds such as the lactic acid pair described above has
a long list of identical properties: the two Enantiomers have exactly the same melting
points, NMR and IR spectra, Rf values on TLC, and retention times on GC. Thus, as you
might expect, only subtle physical differences exists between a pair of enantiomers, making
them difficult to separate. The physical property that differentiates enantiomers is their
ability to rotate plane-polarized light. One member of an enantiomeric pair always rotates
plane-polarized light to the right (this compound is said to be a positive rotation, or to be
dextrorotatory); the other member of the pair always rotates plane-polarized light to the left
(this compound has a negative rotation; thus, it is levorotatory). Moreover, the rotations of
an enantiomeric pair, although opposite in sign, are always equal in absolute magnitude.
Thus, the lactic acids have two specific rotations of +3.82o and -3.82o.
The basic concepts of stereochemistry can be extrapolated to larger molecules, and
you will do this in a hands-on fashion by using molecular models. It is possible to have a
number of stereocenters in a compound; but, for optical activity, there must be no plane of
symmetry. A large number of stereoisomers are possible for molecules with a high number
of chiral centers, but the basic principles described here and developed in the following
molecular modeling exercise always hold true.
The importance of stereochemistry can be made clear by considering a number of
biologically related examples. First, the two lactic acid structures shown earlier have
different origins. The dextrorotatory (+) form exists in blood and in muscle fluid. The
levorotatory (-) form is half of the racemic mixture found in sour milk and in some fruits
and plants. A racemic mixture is a 1:1 mixture of the dextro- and levorotatory forms and is
indicated by the symbol (±). Nature provides both forms of carvone shown here. (+)Carvone is isolated from caraway seeds and has a distinctive caraoil way smell. (-)Carvone is isolated from spearmint leaves, and is used as flavoring in spearmint candies,
toothpaste, etc. The two enantiomers smell completely different because the receptor sites
for the sense of smell in our noses are chiral. Just like the left hand that doesnʼt fit into a
right-handed glove, (+)-Carvone doesnʼt fit into the receptor site that identifies spearmint
smell. Finally, the structure of L-dopa is of interest. This compound is a significant antiParkinsonian drug; but its enantiomer, D-dopa, has no therapeutic effect. The receptor site
that L-Dopa in the brain is also chiral.
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CH3
O
H
O
CH3
HO
H
(+)-Carvone (-)-Carvone
HO
COOH HOOC
H
NH2
H2N
L-Dopa
OH
H
OH
D-Dopa
Making Models with a Molecular Model Kit
Molecular models are helpful, sometimes even essential, for visualizing the threedimensionality of molecules. In this "experiment" models will be used to illustrate the
various conformations of molecules.
This exercise is designed to be done with your molecular model kit during a
regularly scheduled laboratory period. Your report should include solid/dashed-wedge
structures, and answers from each question.
The models used in this experiment show the correct angles between chemicals
bonds, but they do not accurately show the relative sizes of atoms or the correct bond
lengths. Nevertheless, they help us to appreciate the different possible arrangements of
the atoms in a molecule, the different shapes that a molecule can assume, and the ways
in which these shapes can be represented by two-dimensional formulas. Identify what the
different colored balls represent (i.e. black is a carbon atom) and what the different bond
lengths signify.
DEFINITIONS
It will be helpful to define a few terms related to symmetry, because we will be
examining the symmetry properties of the molecular models we construct.
Absolute configuration - The actual three-dimensional arrangement of a molecule or of a
chiral center. This arrangement is often determined by X ray analysis and is properly
labeled with R/S notation.
Asymmetric - Without symmetry or devoid of any symmetry.
Chirality - The property of handedness. Your hands are chiral.
Conformer (or Conformational Isomers) - Conformers are various forms of a single
molecule that can be interconverted without breaking bonds. This can be done without
breaking bonds. They can be interconverted by rotation about single bonds, as well as by
bending or folding molecules.
Diastereomers (or Diastereoisomers) - Two molecules that are stereoisomers but not
enantiomers. the 2S,3R and 2R,3R molecules in 2-bromo-3chlorobutane are
diastereomers.
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Enantiomers - Molecules that are mirror images but not superimposable.
Isomers - molecules that have the same molecular formula but different structures.
Meso Form - A molecule that contains one or more molecular planes of symmetry, in spite
of having two or more chiral centers.
Optical Activity - The ability of molecules to rotate plant-polarized light. Only molecules
that are chiral can display optical activity.
Plane of Symmetry - A plane that can be imagined to pass through a molecule so that
the part of the molecule on one side of the plane is the mirror image of the part on the
other side. In other words, a plane of symmetry is a mirror plane. For example if a
molecule had the exact shape of a sphere, then any plane that passed through the
center of the sphere would be a plane of symmetry.
R/S Notation (Cahn-Ingold-Prelog notation)- The assignment of absolute configuration to
chiral atom centers, using priority rules.
Stereoisomers - These are isomers that have the same sequence of bonds and
atoms but differ only in the spatial arrangement of the atoms. Within this general
category are enantiomers and diastereomers. cis/trans-Isomers (or Geometrical
isomers) are classified as diastereomers.
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