MODULE 5 -Stereochemistry CHM036 Organic Chemistry for Engineering Technologist 2020-2021

MODULE 5 - STEREOCHEMISTRY
HANDOUT
The objective of this handout is to enhance the skills of the students to identify and assign
isomers of some organic compounds. Also, it may enable the students to understand better and
appreciate the three-dimensional structure of some organic molecules in biological systems. The
exercises serve to supplement their understanding the concept of stereochemistry.

Basic Concepts
Isomers have the same molecular formula. Constitutional isomers have different
arrangements of the atoms. Stereoisomers are molecules with the same atoms and connectivity, but
different spatial arrangement. Stereochemistry is the study of how atoms in a molecule are arranged
in space.
The following figure illustrates the concept map of isomers. The concept map shows the
interconnections of concepts, as given in the lecture component of the course.

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Chiral and Achiral

A chiral object is not superimposable on its mirror image. Objects that are superimposable
on their mirror images are called achiral objects. The achiral objects contain at least one plane of
symmetry. Carbons with four different groups attached are chiral carbons. They are not
superimposable on their mirror images. Chiral molecules contain one or more chiral centers. Chiral
compound will have two enantiomeric forms (a pair of enantiomers).

Molecules of the type CH3X and CH2XY are identical to their mirror images, but a molecule of the type
CHXYZ is not.

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MODULE 5 -Stereochemistry CHM036 Organic Chemistry for Engineering Technologist 2020-2021

Enantiomers
A molecule and its mirror image are called enantiomers. They contain chiral carbons and are
mirror images of each other which are not superimposable.

A molecule that contains a plane of symmetry will be superimposable on its mirror image and is thus
achiral.

Most, but not all chiral molecules contain asymmetric centers (chiral centers). Carbon contains
four different groups attached to it is an asymmetric center.

Meso Compounds
Meso molecules have more than one stereogenic or chiral center and are achiral (they give a
superimposable mirror image). Meso compounds can be recognized by two or more chiral centers
and contains a mirror plane of symmetry and each chiral center is the mirror image of the other.

This compound has two asymmetric centers,

however, it has a plane of symmetry. This plane of
symmetry makes it achiral. This is by definition a
meso-compound

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This molecule has no plane of symmetry and thus

chiral.

These two molecules represent a pair of diastereomers:

Diastereomers

Molecules with more than one stereocenter give rise to non-enantiomers called
diastereomers. Diastereomers are non-mirror image stereoisomers. The no. of chiral centers, n give
rise to 2n sets of stereoisomers.

Optical Activity
When plane-polarized light is passed through a solution containing one enantiomer, it is
rotated to a certain degree. A dextrorotatory (+) enantiomer gives a positive optical rotation. A
levorotatory (-) enantiomer gives a negative optical rotation

R and S
R and S configurations can be assigned to chiral centers. R is rictus meaning clockwise and S
is sinister meaning counterclockwise. Enantiomers are assigned either R or S based on the spatial
arrangement of the groups on the stereogenic carbon. If one enantiomer is R, its mirror image will
be S.
Sequence Rules for Assigning the R and S Configuration:
Chiral centers can be assigned an R or S configuration based on the arrangement of the four
different groups around the chiral center. This allows one to name each enantiomer in a pair
unambiguously as shown below for the two 2-chlorobutane enantiomers.

1. Look at the four atoms directly attached to the asymmetric center.

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2. Prioritize these atoms based on atomic number

• If there is a tie between two or more groups, move out to the next atom in each chain
and compare.

• Atoms with a double or triple bond are treated as having two (or three) bonds to
phantom atoms.

• When two carbons have substituents of the same priority, but one has more of the
priority substituents, this carbon is given priority.

4. Orient molecule so that the lowest priority group (group 4) is pointing to the back.
5. Draw a curved arrow from group 1 2 and from 2 3.
6. Determine configuration based on the direction of the curved arrows.

Example 1:

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MODULE 5 -Stereochemistry CHM036 Organic Chemistry for Engineering Technologist 2020-2021

Example 2:

Fischer Projections
Fischer projections are another drawing style that is used to represent the three-dimensional
structure of acyclic molecules. Each cross in a Fischer projection typically represents a chiral center.
By definition, in a Fischer projection, the horizontal bonds are considered to be coming out of
the page while the vertical bonds are considered to be going back into the page (horizontal
bonds are in front of the plane and vertical bonds are behind the plane).

To convert a molecule with more than one chiral center into a Fischer projection:
• you must first identify the main backbone that will be the vertical axis in the Fischer
projection (highlighted in blue in the example below);
• next you must rotate the bonds so that the vertical axis is pointing away from the viewer.
Basically, the main carbon backbone is positioned such that it curves away from the viewer;
• next, to get the main chain in a vertical orientation, the entire molecule is then rotated 90° to
the right. This representation can then be rotated around an axis to put the vertical groups
back and the horizontal group out;
• finally, flattening the molecule gives the Fischer projection.

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Manipulation of Fischer Projection

1. Fischer Projection can be rotated by 180 ° only.

Rotation by 90 ° or -90 ° (270 °) invert the stereochemistry

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2. If one group of the Fischer projection is held steady, the other groups can be rotated either
clockwise or counter clockwise.

Assigning R and S-configurations to Fischer projections

1. Assign priorities to the four substituents according to the Cahn-Ingold-Prelog convention.
2. Perform the two allowed manipulations of the Fischer projection to place the lowest priority group
on one of the vertical positions (either top or bottom)
3. If the priorities of the other three groups (1-2-3) proceed clockwise, the stereogenic center is
assigned as R. If the priorities of the other three groups (1-2-3) proceed counter clockwise, the
stereogenic center is assigned as S.

For more structures with more than one stereogenic center such as carbohydrates, the tetrahedral
carbons are "stacked" on top of one another.

Stereoisomers can be represented easily using Fischer projections. In the example below, A
and B represent a pair of enantiomers as does C and D. A and C, A and D, B and C, and B and D,
all represent pairs of diastereomers because they are non-superimposable and are not mirror images.

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For carbohydrates, the convention is to put the carbonyl group at the top for aldoses and closest to
the top for ketoses. The carbons are numbered from top to bottom.

Carbohydrates and amino acids are designated as D- or L- according to the stereochemistry

of the highest numbered carbon in the Fischer projection. If the hydroxyl group (or amino group for
amino acids) is pointing to the right in the Fischer Projection, the sugar (or amino acid) is designated
as D. If the hydroxyl group (or amino group for amino acids) is pointing to the left in the Fischer
projection, the sugar (or amino acid) is designated as L. Most naturally occurring carbohydrates are
of the D-configuration while most naturally occurring amino acids are L.

Converting Fischer Projections into Haworth Projections.

1. Identify the hydroxyl group which is cyclizing onto the carbonyl group. This hydroxy will become
the ring oxygen in the hemiacetal or hemiketal form of the carbohydrate. For D-glucose, it is the
C5 hydroxyl in the pyranose form; for D-ribose, it is the C4-hydroxyl for the furanose form.
2. Manipulate the Fischer projection so this hydroxyl group is on the bottom.

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3. Draw the Haworth projection so that the ring oxygen is on the top. For pyranoses, draw the six-
membered ring laying on it side with a oxygen at the upper right.
4. Substituents on the right side of the Fischer projection will be on the bottom face of the
Haworth projection. Substituents on the left side of the Fischer projection will be on the top face
of the Haworth projection.
5. Remember that in the cyclic form, the C1-hydroxyl group (the anomeric center) can usually
adopt either the up or down configuration.

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