Chapter 9 Stereochemistry

Stereochemistry is the study of the physical and chemical consequences of 3D molecules.

I. Isomers are molecules with the same formula but different structural or special features.

1. Structural (Constitutional) ~ same formula, different structure

a. Compounds which differ in the connectivity of atoms; the skeleton is different.
b. Are different compounds with different physical and chemical properties.

i. Tautomers are constitutional isomers which spontaneously interconvert

and that differ in the placement of a hydrogen atom
a. Keto-Enol Tautomerism

55
2. Sterioisomers—compounds whose atoms are connected in the same order, but with
different geometry
a. Conformational Isomers—spontaneously interconvert through a rotation about a
sigma bond

b. Enantiomers—pair of molecules which , even though they reflect one

another, are non-superimposable mirror images that exhibit identical physical
properties

c. Diasteromers—pair which are not enantiomers (those which are not mirror
images of each other) that exhibit different physical and chemical properties

i. Cis/Trans isomerism

56
 Enantiomers have opposite configurations at ALL chiral centers, while
Diasteromers have opposite configurations at SOME chiral centers

II. Chirality

A Plane of Reflection is an imaginary plane, which bisects a molecule such that there is a
reflection within a molecule. All molecules belong to two classes

1. Achiral—a plane of reflection exists if a molecule is achiral, it has a plane of

reflection; its mirror image is an identical molecule

2. Chiral—no plane of reflection if a molecule is chiral, its mirror image is non-

superimposable meaning the molecule and its mirror image are enantiomers

56
An atom with tetrahedral geometry (carbon is sp3 hybridized) and has four different ligands
(atoms, groups, electrons) is called the chiral center

If a molecule has a chiral center, this molecule and its mirror image WILL BE ENANTIOMERS

Compounds that are ACHIRAL, yet contain chirality centers are called meso compounds
– Even though there are chiral centers in the molecule, because of a symmetrical plane, the
molecule contains one less enantiomers and is called meso

III. R/S Classification for Chiral Carbons

1. Assign Priority of Atoms/Groups attached to a tetrahedral seteriocenter
a. For different elements, higher atomic number takes priority
i. X > O > N > C >H
b. In the case of carbon vs. carbon—differentiate at nearest point of difference
i. A carbon with a heteroatom attached beats one without
ii.For carbons with no heteratoms, one with the more Hs loses
c. Handling double and triple bonds

56
 i. Double and triple bonds are treated as if each of the bonds has extra C’s
attached
2. If lowest priority group is in the back, trace a path from 1—2—3
a. If path goes clockwise, steriocenter is R
b. If path goes counterclockwise, steriocenter is S
3. If lowest priority group is in the front, trace a path
a. If path goes clockwise, steriocenter is S
b. If the path goes counterclockwise, steriocenter is R
4. If lowest priority group is to the left or right, exchange it with the group in the back
and trace the resulting figure
a. If the path goes clockwise, the steriocenter is S
b. If the path goes counterclockwise, the steriocenter is R
5. In Fisher projections, since H is always in front, clockwise is S and counterclockwiseis R

Fisher Projections are planar representations, but with specific meaning:

a. Horizontal bonds are coming OUT of the plane
b. Vertical bonds are BEHIND the plane, so:

Position of lowest Priority Clockwise Counterclockwise

Back R S
Front S R
Left/Right ExchangeS ExchangeR
Fisher S R

IV. Consequences of Chirality

Enantiomers exhibit identical physical and chemical properties except under chiral conditions

Basic Chiral Rules with hands as examples

1. Right and left hand are chiral, non-superimposable mirror images; they are akin to a pair
of enantiomers
2. Both hands can do the same things; under achiral conditions the right can’t be
distinguished from the left
a. Achiral: a box—you put both hands into a box and they both fit equally
b. Achiral: Flat mittens can be work on either hand
c. Chiral: A right handed glove; the glove selects for the right hand
i. Enzyme drug interactions are often specific as a hand-in-a-glove
ii.Enzymes ‘select’ which enantiomers to react with

Separation of enantiomers
55
Generally, when separating components, we use Silica Gel (Column Chromatography); however
we can’t use it in this case. Therefore, we have to use chiral silica

To separate enantiomers, their reflection plane must be broken.

Example:

56
In general, the number of sterioisomers possible = 2n; where n = number of chiral center
So, in the above examples there were two chiral centers, so 22 = 4 sterioisomers possible

Example:
3 chiral centers  8 sterioisomers possible (4 pairs)

57
IV. Optical Activity

1. Plane Polarized Light

One physical property where enantiomers differ is their rotation of plane polarized light.
Plane polarized light, which is generated by a polarimiter, vibrates in only one plane

2. Interactions of plane polarized light with chiral molecules

a. Chiral molecules are optically active because of their interactions with plane polarized
light
b. A pair of enantiomers are sometimes called optical isomers
c. Under identical conditions, R and S enantiomers have rotations that are equal in
magnitude, but opposite in sign

d. Neither the direction nor the magnitude can be predicted; they have to be determined
experimentally
e. Achiral molecules give zero rotation
f. A 50:50 mixture of R and S will give zero rotation; such a mixture is called a racemate
or racemic mixture
g. Nomenclature
i. (+)- or (-)- is designated before the name
i. d = dextrorotary (rotates to the right ; +)
ii.l = levorotatory (rotates to the left; -)

2. Specific Rotation is the optical rotation of a sample; it is given by the formula

[α]D25=αc*l where α = observed rotation
c = concentration (g/mL)
l = pathlength (dm)

58
Example: A 20g sample of R enantiomers is dissolved in 10mL of water. This solution gives a
rotation of +100 degrees when using a 1dm polarimiter tube.
a. What is the specific rotation of this enantiomers?
b. What is the specific rotation of its S enantiomers?

1. Optical Purity (Enantiomeric Excess) is a measure of the molar ratio of enantiomers

present in a mixture

V. Reactions at Chiral Centers

1. Inversion of configuration due to a backside attack like in an SN2 Reaction

2. Racemization is the loss of the chiral center like in a SN1 Reaction (the partial conversion of
one enantiomers into another; the intermediate is not chiral)

56
3. Retention of configuration

4. Enrichment (results in an R/S mixture that is something other than racemic)

56
57