Download Chem 341 • Organic Chemistry I

Chem 341 • Organic Chemistry I
Lecture Summary 25 • October 24, 2007
Chapter 9 - Stereochemistry
Chirality
Many molecules in nature are ‘handed’. That is, they can exist as a special kind of stereoisomer
that we call Enantiomers. Enantiomers are compounds that are mirror images and are not
superimposable on each other (not identical). Just like you have a left-hand and a right-hand,
some molecules are Chiral. (Note that molecules that are identical with their mirror images are
called achiral.) Due to the tetrahedral nature of sp3-hybridized carbons, if all four groups on a
carbon are different, their mirror images are not identical. See below, for example, a simple
methyl group with four different colored groups attached. It’s mirror image is a different
molecule. If you try to line them up and superimpose them, you weill find that two of the colors
do not match up. Thus, this is a chiral molecule.
Chirality and Biology
The molecules of living systems are made up mostly of compounds that contain these type of
stereogenic carbons - carbons with four different groups attached. Mainly these include sugars
which make up the backbone of DNA and amino acids which are the basic structures of
proteins. Thus, biological processes rely on the interactions of chiral molecules. Many drugs
only work by fitting one enantiomer of the drug into an enzyme receptor like a key in a lock. A
classic example of this is the tradegy of the drug, thalidomide. This drug was made as a 50:50
mixture of enantiomers and given to pregnant women to ease morning sickness. One
enantiomer of the drug had the beneficial effects while the mirror image caused severe birth
defects.
©2007 Gregory R. Cook
North Dakota State University
page 1
Chem 341
O
stereogenic
carbon
O
N
*
O
stereogenic
carbon
N
*
O
N
H
O
(R)-thalidomide
beneficial sedative
O
N
H
O
O
(S)-thalidomide
causes birth defects
Optical Activity
Enantiomers have identical physical properties in all respects but one. Their ability to rotate the
plane of plane polarized light. All other properties such as melting points, boiling points,
spectroscopic absorptions, etc. are all identical. As shown below, when light is passed through
a polarizing filter the waves are all traveling in one plane. When those light waves strike a chiral
molecule, the plane of the waves as they travel through are rotated. What you see if you are
looking directly at the light as it comes toward your eye would be a rotation to the left or right
from the original plane. Enantiomers will rotate the light an equal amount in opposite directions.
Samples that rotate plane polarized light are said to be “optically active”. Achiral molecules do
not rotate the plane of polarized light.
light travels in
waves but
oscillates in all
three dimensions
along the path of
travel
Light is polarized
and oscillates in a
single dimension
when the polarized
light passes
through a chiral
sample, it is bent
out of the original
plane
chiral
sample
Note that the
enantiomer will
bend the light in the
opposite direction
chiral
sample
enantiomer
polarizing
filter
A racemic mixture of enantiomers is a 50:50 mixture of the mirror images. A racemic mixture will
not be optically active as they rotation of plane polarized light will be exactly cancelled out by
the presence of both enantiomers in equal amounts. Mixtures of enantiomers that are not equal
amounts will show rotation of plane polarized light in the amount of the excess of one
enantiomer over the other. That is, the effect will not be completely cancelled out.
R and S Configurations of Stereocenters
As enantiomers are stereoisomers that are only different at the asymmetric carbon (stereogenic
carbon), we need a way to distinguish them in the name. We use the Cahn-Ingold-Prelog
priority rules (as we did with E and Z) to assign a ranking of priority to the four different groups.
If we visualize the molecule pointing the lowest priority group away (usually H) the three
remaining groups define a circle. If you travel from highest priority (1) to lowest (3) you will go
clockwise in the R-enantiomer whereas you will travel counterclockwise in the S-enantiomer.
©2007 Gregory R. Cook
North Dakota State University
page 2
Chem 341
You can also use your hands to help you by pointing your thumb toward the lowest priority
group and seeing which hand you need to curl your fingers from highest priority to lowest
priority. The right hand would be the R-enantiomer (latin - rectus = right) and the left hand would
be the S-enantiomer (latin sinister = left).
4
H
3
Cl
1
1
2
(R)-2-chlorobutane
2
Cl
H
4
3
(S)-2-chlorobutane
Quiz of the day
©2007 Gregory R. Cook
North Dakota State University
page 3
Chem 341