STEREOCHEMISTRY

Stereochemistry is the study of the three-dimensional structure of molecules.

Isomers are grouped into two classes: constitutional isomers and stereoisomers.

Constitutional isomers (structural isomers) differ in their bonding sequence and their
atoms are connected differently which includes skeletal, functional, and positional
isomers.
Different carbon skeletons

2-methylpropane butane
Different functional groups CH3CH2OH and CH3OCH3
Ethanol methoxymethane

Different positions of
functional groups

2-propanamine propanamine
Stereoisomers are compounds that have the same atom connectivity but a different
arrangement of atoms in space.

3D representation

Geometric isomerism
butene and 2-butene are position isomers because in these compounds the double
bond has a different position in the carbon chain:

But the 2-butene may also exhibit stereoisomerism. There are two stereoisomers of 2-
butene that differ in the geometric arrangement of the groups attached to the double
bond. In one isomer, both methyl groups are on the same side of the double bond (cis-
2-butene) and in the other, the methyl groups are on opposite sides of the double bond
(trans-2-butene):
Stereoisomers that do not interconvert rapidly under normal conditions, and are stable
enough to be separated are called configurational isomers. The cis- and trans-2-
butene and cis- and trans- l,2-dimethylcyclopropane are configurational isomers. The
terms cis-trans isomerism or geometric isomerism commonly are used to describe
configurational isomerism in compounds with double bonds and rings. When we refer
to the configuration of a particular isomer, we specify its geometry.
Chirality
For an object to have a property of chirality there must be no plane of symmetry in the
object. If there is a plane of symmetry the object will non-chiral and superimposable
on its mirror image. Examples of chiral objects: hands, feet shoes
Examples of non-chiral: gloves, spoon, socks

Organic molecules are either chiral (different from their mirror image )or achiral
identical to their mirror image. For the two geometric isomers of 1,2-
dichlorocyclopentane, the cis isomer is achiral because its mirror image is
superimposable on the original molecule. Two molecules are said to be
superimposable if they can be placed on top of each other and the three-dimensional
position of each atom of one molecule coincides with the equivalent atom of the other
molecule.
But the trans-l ,2-dichlorocyclopentane exhibits mirror image, different from (non-
superimposable with) the original molecule. Nonsuperimposable mirror-image
molecules are called enantiomers. A chiral compound always has an enantiomer (a
non-superimposable mirror image). An achiral compound always has a mirror image
that is the same as the original molecule.
Two kinds of stereoisomers
1. enantiomers – stereoisomers that non-superimposable on their mirror images
Enantiomers occur only with compounds whose molecules are chiral.
The relationship between a chiral molecule and its mirror image are said to be
enantiomers of each other.

2. diastereomers- these are stereoisomers that are not mirror images and are non-
superimposable; they are stereoisomers that are not enantiomers.

A molecule that has a carbon attached to four different groups of atoms is chiral and
will exist as two different enantiomers.
a carbon atom is called an asymmetric carbon atom or a chiral carbon atom and is
often designated by an asterisk (*).

Note: Asymmetric carbon atoms are examples of chirality centers which are
examples of stereocenters.
Examples:

The most common cause of chirality in organic molecules is a tetrahedral carbon

atom with four different groups bonded to it and such a chiral carbon atom is a
stereocenter. 2-Butanol has one stereocenter while 2- propanol has none.
Practice Exercise 1
Draw the structural formula of the following and place an asterisk on the chiral
carbon
a. propanoic acid
b. 2-hydroxypropanoic acid
c. 2-Chloropentane
d. 3-Chloropentane
e. 3-Chloro-1-butene
f. 1,2-Dichloropropane
g. 2- pentanol
h. pentanol

(R) and (S) Nomenclature of Asymmetric Carbon Atoms

Alanine or 2-aminopropanoic acid has an asymmetric carbon atom, and it exists in
two enantiomeric forms.

These mirror images are different and only the natural alanine can be metabolized by
the enzyme in our body while the unnatural alanine is not recognized as a useful amino
acid. The difference between these two enantiomers of alanine lies in the three-
dimensional arrangement of the four groups around the asymmetric carbon atom. Any
asymmetric carbon has two possible (mirror-image) spatial arrangements, known as
configurations. The alanine enantiomers represent the two possible arrangements
of its four groups around the asymmetric carbon atom.
The Cahn-Ingold-Prelog convention is a widely accepted system for naming the
configurations of chirality centers. Each asymmetric carbon atom is assigned a letter
(R) or (S) based on its three-dimensional configuration. To determine the name, we
assign "priorities" to the four substituents and then assign the name based on the
positions of these substituents.
Steps:
1. Assign a "priority" to each group bonded to the asymmetric carbon:
group 1 as having the highest priority, group 2 second, group 3 third, and group
4 the lowest priority. Priority is based on atomic number: The higher the atomic
number, the higher the priority.
R,S Priorities of Some Common Groups.

2. In case of ties, use the next atoms along the chain of each group as tiebreakers.
For example, we assign a higher priority to isopropyl -CH(CH3)2 than to ethyl -
CH2CH3. The first carbon atom in the ethyl group is bonded to two hydrogens and
one carbon, while the first carbon in the isopropyl group is bonded to two carbons
and one hydrogen. An ethyl group and a -CH2CH2Br have identical first atoms and
second atoms, but the bromine atom in the third position gives -CH2CH2Br a higher
priority than -CH2CH3. One high-priority atom takes priority over any number of
lower-priority atoms.
3. Treat double and triple bonds as if each were a bond to a separate atom. Imagine
that each pi bond is broken and the atoms at both ends are duplicated. Note that
when you break a bond, you always add two imaginary atoms.

4. Using a three-dimensional drawing or a model, put the fourth-priority group in

back and view the molecule along the bond from the asymmetric carbon to the
fourth-priority group. Draw an arrow from the first-priority group, through the
second, to the third. If the arrow points clockwise, the asymmetric carbon atom
is called (R) (Latin, rectus, "upright"). If the arrow points counterclockwise, the
chiral carbon atom is called (S) (Latin, sinister, "left").
 Practice Exercise 2
a. Draw the enantiomers of 1,3-dibromobutane and label them as (R) and (S).
b. Place an asterisk on each asymmetric carbon atom in the following examples, and
determine whether it has the (R) or (S) configuration.

How Many Stereoisomers Are Possible for Molecules with Two or More
Stereocenters?
For a molecule with n stereocenters, the maximum number of stereoisomers
possible is 2n. For a molecule with one stereocenter, 2 stereoisomers (one pair of
enantiomers) are possible. For a molecule with two stereocenters, a maximum of 22 =
4 stereoisomers (two pairs of enantiomers); for a molecule with three stereocenters, a
maximum of 23 = 8 stereoisomers (four pairs of enantiomers), and so forth.

Molecules with Two Stereocenters

There are 2 stereocenters for the compound 2,3,4-trihydroxybutanal

therefore 4 possible stereoisomers or two pairs of enantiomers.

Types of Projections
(a) and (b) and (c) are the two pairs of enantiomers
(a) and (c), (a) and (d), (b) and (c), and (b) and (d) are diastereomers—
stereoisomers that are not mirror images.
Example: Draw all the possible stereoisomers for the compound 1,2,3-butanetriol.
(a) Which stereoisomers are pairs of enantiomers?
(b) Which stereoisomers are diastereomers?
Practice Exercise 3
1. Which of the following compounds contain stereocenters?
(a) Cyclopentanol
(b) Chloro-2-propanol
(c) 2-Methylcyclopentanol
(d) Phenyl-1-propanol
2. Label all stereocenters in each molecule with an asterisk. How many
stereoisomers are possible for each molecule?

c.
b.
a.

2. Draw all the possible stereoisomers for the 3-amino-2-butanol

(a) Which stereoisomers are pairs of enantiomers?
(b) Which stereoisomers are diastereomers?
Optical Activity
Mirror-image molecules have nearly identical physical properties as can be seen
from the table below.

Properties of Enantiomers: Optical Activity

Enantiomers have identical physical properties such as boiling points, melting points,
refractive indices, and solubilities in common solvents except optical rotations.
Enantiomers rotate the plane of plane-polarized light in equal amounts but in
opposite directions.
Plane-Polarized Light
The light used to measure optical activity has two properties: consists of a single
wavelength and it is plane-polarized.
Optical activity is the ability of a chiral substance to rotate the plane of plane-
polarized light and is measured using an instrument called Polarimeter.
A polarimeter measures the rotation of plane-polarized that has passed through a
solution.
Dextrorotatory: Clockwise rotation of the plane of plane-polarized light. Indicated by
(+).
Levorotatory: Counterclockwise rotation of the plane of plane-polarized light.
Indicated by (-).
Specific rotation: The observed rotation of an optically active substance at a
concentration of 1 g/mL in a sample tube 10 cm long.
specific rotation []

When one of the enantiomers of 2-butanol is placed in a polarimeter, the observed

rotation is 4.05° counterclockwise. The solution was made by diluting 6 g of 2-
butanol to a total of 40 mL, and the solution was placed into a 200-mm polarimeter
tube for the measurement. Determine the specific rotation for this enantiomer of 2-
butanol
Given:
 observed= -4.05
Concentration = 6g/40 mL= 0.15 g/mL
L= 200 mm=2 dm

Meso Compound
An achiral compound with chirality centers but has a plane of symmetry.
Tartaric acid has two chirality centers: One form is chiral and the other is achiral, but
both have two chirality centers.

There are only three stereoisomers of 2,3-dibromobutane because two of the four
structures are identical.
Racemic Mixtures
A 50:50 mixture of two enantiomers causes no net rotation of plane-polarized light or
optically inactive. A racemic mixture is symbolized by placing (±) or (d,l) in front of
the name of the compound. For example, racemic 2-butanol would be symbolized by
"( ± )-2-butanol" or "(d,l)-2-butanol."
Practice Exercise 4
1. A solution of 2.0 g of ( + )-glyceraldehyde, HOCH2 -CHOH -CHO, I n 1 0 mL of
water was placed in a 1 00-mm cell. Using the sodium D line, a rotation of + l .74° was
found at 25° C. Determine the specific rotation of (+ )-glyceraldehyde.
2. A solution of 0.5 g of ( -)-epinephrine dissolved in 10 mL of dilute HCI was placed
in a 20-cm polarimeter tube. Using the sodium D line, the rotation was found to be -
5.0° at 25° C. Determine the specific rotation of epinephrine.
3. Determine which of the following compounds are chiral. Place an asterisk on an
asymmetric carbon atom, and draw in any mirror planes. Label any meso compounds.