CHEM 3331
CH 5: Stereochemistry
Stereochemistry is the study of 3- dimensional structure of molecules
Isomers
Constitutional (structural)
 Same formula
 Different
connectivity
Do not cover:
Section 5
Section 7- e.e/ opt purity
Section 16- resolution of enantiomers
Stereoisomer
 Same formula,
same connectivity
 Different spatial
arrangement
Configurational
Cannot be interconverted
unless bonds are broken
Enantiomers
Mirror images that are
not superimposable
Diastereomers
Config. isomers that
are NOT mirror images
(includes cis/trans
isomers)
Conformational
Rapidly interconverts
without breaking bonds,
usually cannot isolate
C—C single bond
rotation
conformers
etc.
1. Introduction and Definitions
In this Chapter, we will be talking about enantiomers.
In 1843 Pasteur found that one can separate crystals of racemic tartaric acid into two compounds that are
mirror images of one another. A solution from one of these crystals rotated polarized light into one direction,
other solution from other crystals rotated light into another direction.
Pasteur had discovered that some compounds may exist as pairs of enantiomers.
Compounds are enantiomers of each other if they are non-superimposable mirror images of each other.
With some exceptions, carbon atom needs to have 4 different substituents to attain a mirror image that is not
super imposable.
But if 2 or more substituents are the same, then mirror images are superimposable
Difficult to see without models!!!
Definitions:
Chiral (handed)—different from its mirror image; having an enantiomer.
Achiral (not handed)—identical with its mirror image; not chiral
Chiral or achiral molecule? :
Need to make distinction between chiral molecules and chiral or asymmetric carbon atoms.
Chiral or asymmetric carbon atoms is a carbon atom to which 4 different groups are attached. Chiral C atoms is
the most common example of a chirality center or stereocenter. Stereocenter is any atom of which exchange of
2 groups gives a stereoisomer.
Molecules may be chiral and have no chiral carbon
Molecules may contain chiral carbon atoms and still be achiral (later)
Generalization:
1. If a compound has no asymmetric C atom, it is usually achiral.
2. If a compound has just one asymmetric atoms it is always chiral.
3. If a compound has more than one asymmetric C, it may or may not be chiral.
What happens in molecules with more than one asymmetric carbon atom?
cis
achiral- mirror images are the same
Any molecule that has an internal mirror plane of symmetry cannot be
chiral even though it contains asymmetric C atoms.
trans
What about these?
How many chiral C atoms? :
2. R, S Nomenclature
Naming enantiomers
Cahn-Ingold-Prelog convention used
1. Assign a “priority” to each group bonded to asymmetric carbon
a. The higher atomic number of element, the higher the priority
Look only at atom directly bonded to the asymmetric carbon
With different isotopes, heavier isotopes have higher priority
e.g. 2H (deuterium, or D) higher priority than 1H.
b. In the case of ties, use next atoms along the chain as tie breakers
Go down the chain until see difference
CH2CH3 and CH2CH2Br have identical 1st CH2, 2nd CH2
but 3rd atom is Br in one case, H in another
c. treat double and triple bonds as if each were a bond to a separate atom (can call this a creation
of “dummy atoms”)
EX:
Using 3-dimensional drawing or model, put fourth priority group in back and view molecule along the bond from
asymmetric carbon to the 4th priority group
A1 > B2 > C3 > D4
Draw arrow starting from 1st
priority group to 2nd to 3rd
R- (right) if arrow clockwise
How do we rotate?
Rule is : keep 1 bond (in this case B—C) fixed. Exchange the position of ALL three other atoms.
Other enantiomer – get if exchange positions of 2 groups
(S) –sinister- if counterclockwise
Amino acid alanine
3. Fisher Projections
Outdated ( ≈100 years) way of drawing asymmetric carbon atoms
Rules
1. Main carbon chain is vertical
2. Vertical line represents bonds behind plane (like dashes)
3. Horizontal lines represent bonds in front of plane (wedges)
4. Intersections represent carbon atoms (usually chiral).
5. Most oxidized group (containing most O) is usually placed on top.
6. Fisher projections must not be removed from plane of paper (cannot be picked up and flipped over!)
7. Projections may be rotated in 2 ways:
a. Whole projection may be rotated 180 o
b. One group attached to a chiral carbon may be held steady and 3 other groups may be rotated
clockwise or counterclockwise.
8. Can draw mirror images to get enantiomers
Plane of symmetry, not chiral molecule
And can determine plane(s) of symmetry
9. Arrangement of R, S configuration using Fisher projections. To assign configuration, put lowest priority
group in back.
Need to rotate Fisher Projection
to get H in back
A few Fisher Projection examples
4. Optical Activity
A) Definition, Measurement
Mirror image molecules (enantiomers) have nearly identical physical properties (m.p, b.p, density are the same).
However, they rotate the plane of polarized light in opposite direction. Consequently, this is the way to
distinguish them. Polarimeter is the device for measuring this rotation. What is polarizes light and polarimetry?
– Light usually vibrates randomly in all planes. Plane polarized light vibrates in one plane only, and when
polarized light passes through a solution containing chiral compounds, the plane of polarization rotates.
Rotation of the plane is called optical activity, and substances that rotate this plane are optically active.
from chemistry.msu.edu
Enantiomers rotate plane of polarized light by exactly the same amount, but in opposite direction.
R-2-butanol rotates at + 13.5o clockwise (dextroratory, +)
S -2-butanol rotates at – 13.5o counterclockwise (levorotatory, -)
B) Racemic mixtures
They are mixtures of equal parts of enantiomers (50:50).
Optically inactive—for every molecule giving (+) rotation, there is one giving (-) thus net is 0
Prefix (±)
e.g. : (±)2-butanol or rac-2-butanol
If start with optically inactive reagents and catalyst, get optically inactive products.
e.g.
5. Chirality of Conformationally Mobile Systems
cis-1,2-dimethylcyclohexane
Draw flat compound
Plane of symmetry-- achiral
What if draw chair?
Is this compound chiral?
No—because chair-chair inter-conversion is rapid at RT and consequently we cannot separate them. Any sample
of cis 1,2-dimethylcyclohexane will contain equal amounts of mirror images.
Molecules are not optically active if chiral conformations are in rapid equilibrium with their mirror image; they
are considered achiral.
To determine whether a conformationally mobile molecule can be optically active, consider most symmetric
conformation!
Consider cyclohexane rings as if they are flat, and consider straight-chain compounds in most symmetric
conformation.
BrCH2CH2Br
Conformational enantiomers
Some molecules cannot convert from one chiral conformer to another.
Example:
For these biphenyls to be chiral need 3 non-hydrogen substituents and A ≠ B, A’ ≠ B’ but A can be = A’ B can
be = B ’
Allenes are also chiral
A≠B
trans-cyclic olefins chiral e.g. cyclooctene (Fig 5-18 in book)
6. Diastereomers
STEREOISOMERS- isomers whose atoms are bonded together in same order but differ in how atoms are oriented
in space. Enantiomers are mirror images of one another.
DIASTEREOMERS- stereoisomers that are not mirror images. Most diastereomers are either geometric (cis/trans)
isomers or compounds containing 2 or more chirality centers.
Diastereomers of molecules with 2 or more chirality centers:
One can also draw them as
Diastereomers have different physical properties (mp, bp, etc.) as opposed to enantiomers
Meso Compounds
Compounds that are achiral even though they have asymmetric carbon atoms are called meso compounds
Examples:
7. Absolute and Relative Configurations
We say that we know the absolute configuration if we know the detailed stereochemical picture of a molecule,
and if we know the arrangement of atoms in space. Another way of saying it is that we need to know R or S
configuration at every center.
Relative configuration is the experimentally determined relationship between the configuration of 2 molecules
even in we do not k now about conf. of each other.
No reaction at chiral C atom so configuration at C is the same + OH and – Br have the same relative
configuration.