Ch15.5−p1
Chapter 15.5 Chiral Molecules
Isomers Revisited
Recall in Chapters 11 and 12 we looked at Constitutional
isomers, molecules that have the same molecular formula
but different arrangement of atoms. We are now going to
look at another class of isomers called stereoisomers. As
you will see shortly, stereoisomers are very important in
organic chemistry. Stereoisomers are molecules that have
the same molecular formula and the same arrangement of
atoms but differ only in the arrangement of their atoms in
space. Stereoisomers can be subdivided into two general
categories: enantiomers and diastereomers.
Enantiomers are stereoisomers whose molecules are
nonsuperimposable mirror images of each other.
Diastereomers are stereoisomers whose molecules
are not mirror images of each other.
Recall cis-trans isomers:
Cl
H
Cl
H
cis-1,2-dichlorocyclopropane
Cl
H
H
Cl
trans-1,2-dichlorocyclopropane
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Do they have the same molecular formula?
Do they have the same connectivity?
Do their atoms have the same orientation in space?
Are they mirror images of each other?
Therefore, the cis-trans isomers of 1,2dichlorocyclopropane are_____________________.
Chirality.
If you hold your hands apart with the palms towards each
other you will see that they are mirror images of each
other. Notice also how your hands are not superposable.
Objects and molecules that have nonsuperimposable
mirror images are said to be chiral. Therefore,
enantiomers can only occur with those compounds whose
molecules are chiral. The word chiral comes from the
Greek word ‘cheir’, meaning “hand”. For this reason
chiral substances are sometimes described as having
‘handedness’. Objects that are superposable on their
mirror images are achiral.
What is the relationship between the following molecules:
H
H
Cl
CH3
CH3CH2
A
CH3CH2
Cl
CH3
B
Ch15.5−p3
They both have the same connectivity so they are either
stereoisomers or identical compounds. In order to find
out we have to determine if their mirror image is
nonsuperimposable.
H
H
Cl
CH3
CH3CH2
CH3CH2
Cl
A
B
H
H
Cl
CH3
CH3CH2
CH3
Cl
H3C
A
CH2CH3
B
H
H
CH3CH2
CH3CH2
Cl
CH3
CH3
Cl
Rotation of molecule B by 120° gives the mirror image of
molecule A. If you superimpose the two molecules you
will find that only two of the substituents line up.
Because these molecules are nonsuperimposable mirror
images of each other they are chiral and enantiomers.
Ch15.5−p4
Is there an easier way to determine if a molecule is chiral?
Fortunately, the answer is yes. A carbon compound is
chiral if at least one carbon atom has four different groups
attached to it. This type of carbon atom is called a chiral
carbon.
e.g. Identify the following molecules as chiral or achiral.
Circle the chiral carbon atoms.
CH3CH2CHBrCH3
H
H3C
CH3CH2
Cl
Cl
H
OH
CH3
Drawing Chiral Molecules.
You have already seen how organic chemists use linebond structures to represent organic molecules. In order
to show the 3-dimentional molecules on paper, they also
use wedge and dash bonds. Wedges are used to show
groups coming out of the plane of the page. Dashes are
used to show groups going into the plane of the page:
H
CH3CH2
Cl
CH3
Ch15.5−p5
Fisher Projections.
Another way to draw stereoisomers is by Fisher
projections devised by Emil Fisher. In this system, bonds
to a chiral centre are drawn as intersecting lines with the
chiral carbon atoms being at the centre where the lines
cross. In order to draw Fisher projections, follow these
rules:
1. The longest carbon chain is drawn vertically with
the most highly oxidized group at the top.
2. Vertical lines are understood to be going into the
plane of the paper.
3. Horizontal lines are understood to be coming out of
the plane of the paper.
4. The letter L designates the left hand isomer; the one
with the –OH group on the left hand side. The letter
D designates the right hand isomer which has the
–OH group on the right side.
Draw the Fisher projection for glyceraldehyde:
O
C
H
CH2
C
HO
OH
H
Turn the molecule so the carbon chain is vertical with the
most highly oxidized carbon on top. In this case the
carbon double bonded to the oxygen atom.
Ch15.5−p6
H
C
O
HO
C
H
CH2
HO
Rotate the molecule counter clockwise out of the plane of
the paper by 90°. Your carbon chain will form a straight
vertical line with the hydroxyl group to the left and the
hydrogen atom to the right. Notice how both the
hydroxyl group and the hydrogen atom are coming out of
the plane of the paper and how the two carbon groups
attached to the chiral carbon are pointing into the plane of
the paper.
H
H
C
O
C
O
HO
C
HO
C
H
H
CH2OH
CH2OH
The Fisher projection would then look like:
H
HO
O
H
CH2OH
Remember, the vertical lines are implied to be going into
the plane of the paper and the horizontal lines coming out
Ch15.5−p7
of the plane of the paper. Since the hydroxyl group
attached to the chiral carbon is on the left hand side we
say that this is the left hand isomer and designate it with
the letter L. Therefore, the Fisher projection that we drew
above is for L-glyceraldehyde. Its enantiomer would be
the mirror image and would have the hydroxyl group on
the right hand side. It is designated with the letter D.
H
HO
O
H
CH2OH
L-glyceraldehyde
O
H
H
OH
CH2OH
D-glyceraldehyde
e.g. Draw the Fisher projection for Lactic acid
CH3CH(OH)COOH
Chirality is a phenomenon that pervades the world we live
in. The human body is chiral with the heart lying slightly
to the left of centre. All but one of the 20 amino acids
that make up proteins are chiral. We speak of nuts and
Ch15.5−p8
bolts as having right- or left-handed threads or a propeller
as having a right- or left-handed pitch. Many plants show
chirality in the way they wind around supporting
structures. Chiral molecules also show their handedness
in the way they biologically affect humans. For example,
one enantiomer of carvone smells like spearmint while the
other enantiomer has the odour of caraway seeds.
Differences in chirality can have much more dire effects
on humans. During the 1960s, the drug thalidomide was
administered to pregnant women to alleviate the
symptoms of morning sickness. However, it was later
found that thalidomide caused horrible birth defects in
many of the children born subsequent to the use of the
drug. We now know that while one enantiomer of
thalidomide has the intended effect of curing morning
sickness, the other enantiomer causes birth defects.
Today, when any drug is placed on the market, it must be
enantiomerically pure.
Ch15.5−p9
Nomenclature of Enantiomers: The (R-S) System.
Because a pair of enantiomers represents different
compounds, they must have different names. So far the
two enantiomers shown below have the same name. In
order to distinguish one enantiomer from the other, we
designate them as either (R) or (S). To designate an
enantiomer as (R) or (S), follow these rules:
Cl
Cl
H3C
H
Br
H
Br
1-bromo-1-chloroethane
CH3
1-bromo-1-chloroethane
1. Assign priority to the four groups attached to the chiral
carbon. Priority is first assigned on the basis of the
atomic number of the atom that is directly attached to the
chiral carbon. The highest atomic number is given
highest priority. When a priority cannot be assigned on
the basis of the atomic number of the atoms directly
attached to the chiral carbon, then the next set of atoms in
the unassigned groups are examined. We assign a priority
at the first point of difference.
b
Cl
c
H3C
Hd
Br a
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2. Place the group with the lowest priority so that it is
pointing away from you.
b
Cl
c
Hd
Br a
H3C
3. Trace a path from a → b → c. If the path you trace is
clockwise, the enantiomer is designated (R). If the
direction is counter clockwise, the enantiomer is
designated (S).
b
Cl
c
H3C
Br a
H
d
The path is counter clockwise therefore the full name for
this enantiomer is (S)-1-bromo-1-chloroethane.
What if the group of lowest priority is not pointing away
you? We can arrange the group of lowest priority to point
away from us if we recognize 2 things:
1.
2.
Exchanging two groups at the chiral carbon inverts
the configuration of the chiral carbon.
A second exchange recreates the original molecule.
Ch15.5−p11
e.g.
What is the IUPAC name for the following molecule?
OH
CH3
CH3CH2
H
1. Assign priorities.
a
OH
CH3
Hd
CH3CH2
b
c
2. Place the group of lowest priority away from us. To
accomplish this, exchange the hydrogen atom and methyl
group. Remember, we have to do a second exchange in
order to regenerate the original molecule. In this case we
will exchange the hydroxyl and the ethyl groups.
CH3CH2
b
a
a
b
OH
OH
CH2CH3
CH3
Hd
c
Hc
CH
d3
CH3CH2
b
3. Trace a path from a → b → c.
b
CH2CH3
a
HO
CH3
c
H
d
a
HO
Hd
CH
c3
Ch15.5−p12
The path is clockwise therefore this enantiomer is
designated (R). The full name for this molecule is (R)-2butanol.
Molecules With More Than One Stereocenter.
So far we have only considered molecules with one
stereocenter. Many organic molecules contain more than
one stereocenter. In order to determine the number of
stereoisomers to expect from molecules with chiral
compounds, use the general formula 2n, where n is the
number of stereocenters. Consider the molecule below:
* *
CH3CHCHCH2CH3
Br Br
This molecule has 2 stereocenters and therefore can have
a maxmimum of 4 (22) different stereoisomers. In order
to find all the stereoisomers, start by drawing a 3dimentional structure for one of the isomers then draw its
mirror image.
CH3
H
H
CH3
Br
Br
H
C
C
C
C
Br
CH2CH3
1
Br
H
CH2CH3
2
Ch15.5−p13
These molecules are two of the four possible
stereoisomers. The other two stereoisomers are shown
below.
CH
CH
3
H
Br
3
Br
Br
H
C
C
C
C
H
CH2CH3
H
3
Br
CH2CH3
4
The compounds represented by structures 1 and 2 are
enantiomers as are structures 3 and 4. What is the
relationship between structures 1 and 3? You must
recognize that 1 and 3 are stereoisomers and that they are
not mirror images of each other. They are, therefore,
diastereoisomers.
Meso Compounds.
A molecule with two stereocenters will not always have
four possible stereoisomers. Some molecules only have
three. This happens because some molecules with more
than one stereocenter are, overall, achiral. Consider the
following molecule:
* *
CH3CHCHCH3
Br Br
Ch15.5−p14
At first glance we would probable think there is four
stereoisomers and draw them as 1, 2, 3, and 4 (below).
CH3
H
CH3
Br
Br
H
C
C
C
C
Br
H
H
Br
CH3
CH3
1
2
CH3
CH3
H
Br
Br
H
C
C
C
C
H
Br
Br
H
CH3
CH3
3
4
Take a closer look at structures 3 and 4. They are in fact
identical compounds. If you rotate structure 4 by 180°
within the plane of the paper, you generate structure 3.
CH3
H
CH3
Br
Br
C
H
C
C
H
CH3
H
C
C
Br
Br
Br
C
H
H
Br
CH3
CH3
CH3
3
4
3
Structure 3 is superposable on its mirror image and is
therefore achiral. Molecules which contain more than
one chiral atom but are overall achiral are called meso
compounds. Another way to test whether a structure is
Ch15.5−p15
achiral is to see if the molecule has a plane of symmetry.
Structure 3(4) has a plane of symmetry which bisects the
two chiral carbon atoms.
CH3
H
Br
C
C
H
Br
CH3
3(4)
Ch15.5−p16
1.
2.
3.
4.
Priority Rules for Assigning cis/trans and R/S
Highest priority goes to the atom with the highest atomic
mass.
If two atoms have the same atomic mass, look at the
atoms attached to each. The one with the heaviest atom
attached gets priority.
If rule #2 does not break the tie, the atom with the larger
number of heavy atoms attached gets priority.
If rule #3 does not break the tie, continue along the chain
(or around the ring) until the tie is broken.