STEREOCHEMISTRY
Stereochemistry is the study of 3-D structures of molecules. For a molecular formula of a
given organic compound, there might be a number of possible structures that can be
drawn. There are usually a number of constitutional isomers (structural isomers), i.e.
isomers with different arrangements of atoms and bonds, e.g. ethanol (CH3CH2OH) and
dimethyl ether (CH3OCH3). In addition, for each of the constitutional isomers, there may
also be the occurrence of stereoisomers. Stereoisomers are isomers which have the same
sequence of atoms and bonds, but differ in the arrangement of the atoms in space, e.g.
.
cis-2-butene
and
trans-2-butene
Presentation of organic molecular structures.
Since organic molecules consist of the element carbon, this discussion will be confined to
the bonding and geometric shapes of carbon compounds. The molecular geometry of a
molecule would depend on the type of hybridized orbitals of the carbon atoms used in
bonding. Carbon atoms using sp- hybridized orbitals for bonding have linear arrangement
of the groups about them. For example, ethyne.
A trigonal planar shaped arrangement is observed when the orbitals which the carbon
atoms used for bonding are sp2-hybridized. An example is ethene.
The orbitals of a sp3-hybridized carbon atom would point towards the corners of a
tetrahedron. For bonding involving sp3 carbons, the angles between the bonded atoms are
approximately 109.50. An example is methane. The perspective formula for methane is
shown below.
Another example is ethane, CH3CH3. Here, we can see two tetrahedral carbon atoms
joined together.
H
H
H
C
C
H
H
H
With more complicated molecules, there are three (3) possible ways to represent the 3-D
structures. Using 2-bromo-3-chlorobutane (CH3CHBrCHClCH3 ) as an example, the 3-D
structures that could be used to represent this molecule is as follows.
(Note: Example shown is only one of the four possible stereoisomers of 2-bromo-3chlorobutane)
1.
Perspective formula
H
H
H
Br
Cl
H
Cl
Br
C
CH3
2.
view
CH3
H3C
C
CH3
perspective f oemula
(eclipsed conformer)
Newman projection
A Newman projection is an end-on-view of only two carbon atoms in the
molecule. The bond joining the two carbon atoms is hidden. The molecule is
viewed from the front. A circle is use to represent the two carbons atoms. The
lines meeting in the center of the circle represent the three bonds attached to the
front carbon. The other three bonds of the rear carbon are shown by lines ending
at the edge of the circle.
CH3
CH3
H
Br
view
H
Br
seen as
Cl
CH3
H
Cl
H
CH3
model of 2-bromo-3-chlorobutane
model viewed end-on
CH3
H
Br
Cl
H
CH3
Newman projection (staggered conf ormer)
Due to free rotation about the sigma bond between the two carbon atoms, the
molecule can assume a number of conformations. Conformers are structures
which differ only by rotations about single bonds, and are usually inter
convertible at room temperature. However certain conformations are more stable
than others. The above Newman projection is a staggered conformer. By rotating
the sigma bond between the two carbon atoms (C2 and C3), an eclipsed
conformer, which is less stable, is formed.
Newman projection (eclipsed conformer)
3.
Fischer projection.
In a Fischer projection, a 3-D molecule is viewed in the eclipsed conformation.
The Fischer projection is a 2-D structure on paper with vertical lines representing
bonds holding atoms projecting away from the observer (into the plane of the
paper). The horizontal lines represent bonds pointing towards the observer (out of
the plane of the paper).
Chiral Compounds
Two possible arrangements of atoms in space for 2-bromobutane are as follows:
Although the two structures initially look identical, but after careful inspection, it can be
seen that they are not actually the same. All attempts to superimpose A and B fail. The
structures are not superimposable. These two structures are not identical, but are mirror
images of each other. Such a pair of structures are called enantiomers. Enantiomers all
have identical physical properties except in their behaviour towards the plane of polarized
light. They would both rotate the plane of polarized light with the same magnitude but in
opposite directions. Compounds that are able to rotate the plane of polarized light are said
to be optically active and are chiral..
Chiral compunds do not have any plane of symmetry (i.e. a plane that can divide the
compound into two equal parts, one the mirror image of the other). If a compound has a
plane of symmetry, then it will be superimposable on its mirror image and will be achiral.
Any compound containing a carbon atom carrying four different groups (asymmetric
carbon atom) will not have a plane of symmetry and must therefore be chiral. Such a
carbon atom is known as a stereogenic or chiral center. The carbon atom marked with an
* in the example below is an asymmetric carbon atom (also known as stereogenic or
chiral center).
The presence of an asymmetric carbon is not a necessary condition for a compound to be
chiral. The absence of a plane of symmetry is an essential feature for a chiral compound.
An example is 1, 3-dibromoallene, Br(H)C=C=C(H)Br.
There is no plane of symmetry in this compound and neither is there an asymmetric
carbon. Since there is no plane of symmetry, the molecule is able to rotate the plane of
polarized light and is therefore a chiral compound.
Configuration of a Chiral Center
One way to differentiate between a pair of stereoisomers is by using a set of rules to
assign a letter R or S to describe the configuration of the chiral atom. To determine the
configuration of the chiral center, first look at the four atoms directly attached to the
chiral carbon and assign priorities in order of decreasing atomic number as in the CahnIngold and Prelog sequence rules (refer to the naming of alkenes in your text book). Then
orientate the molecule so that the atom with the lowest priority is furthest from the
viewer. Finally, mentally trace a path from substituent priority 1 to 2 and 3. If the
direction of the path is clockwise, assign the configuration R to the chiral center; if the
direction is anticlockwise, assign the configuration as S. For example in structure A, Br
is given the highest priority followed by the ethyl group and then the methyl group.
Hydrogen, with the lowest atomic number, has the lowest priority. The chiral center has a
S configuration, so compound A is S-2-bromobutane.
Compounds With More Than One Chiral Center
A compound with only one chiral center is an optically active compound. But there are
compounds with more than one chiral center but are optically inactive because they can
be superimposed on their mirror images. Such compounds are called meso compounds.
Based on the number of chiral carbons in 1,2-dibromobutane there are four possible
stereoisomers. (2n will give the maximum number of stereoisomers possible, where n is
the number of chiral carbons). In actual fact, there are only three stereoisomers because
one of the stereoisomers has a plane of symmetry in the molecule. Its mirror image, on
orientation, will show similar structures to each other (C and D are the same compound).
Eventhough the molecule has two asymmetric carbons, it is able to superimpose on its
mirror image. This makes it an achiral molecule.
Comparing E or F with C/D, it can be seen that they are not superimposable nor are they
mirror images of each other. Such pair of compounds are called diastereomers.
plane of symmetry
CH3
CH3
H
Br
H
Br
H
Br
H
Br
C and D are superimposable because there is
an internal mirror plane in the molecule.
They are the same molecule.
C / D is a meso compound.
CH3
CH3
C
D
diastreomers
diastreomers
CH3
CH3
H
Br
Br
H
Br
H
H
Br
CH3
CH3
E
F
E and F are not superimposable and are miror images.
E and F are a pair of enantiomers.
Cis-Trans Isomers ( geometric isomers)
Cis-trans isomers are also stereoisomers. The substituents are fixed to the same carbon
atoms but they occupy different space. This is due to the presence of a rigid structure
such as a C=C bond or a ring. Alkenes can have cis and trans (or E and Z) stereoisomers,
depending on the relative arrangement of atoms or groups attached to the C═C bond.
The above structures can also be drawn using the perspective formula as follows:
(cis-2-butene)
(trans-2-butene)
The E and Z designations are used when there are no two similar atoms (or groups) on the
C═C bond that could be used for reference at the cis-trans positionings. Before the E and
Z could be assigned, it is necessary to prioritize the different substituents using the CahnIngold and Prelog sequence rules until a distinction is found. Rank substituents in order
of decreasing atomic numbers of the first bound atom. The atom with the highest atomic
number is ranked first. If no distinction is possible at the first atom, consider atoms at
increasing distances until a difference is found. Example:
Z isomer
(Z)-1-bromo-2-chloro-2-fluoro-1-iodoethene
The above molecule is designated as a Z isomer because both atoms with the higher
priority are on the same side of the double bond. If the atoms with the higher priority are
on the opposite sides of the double bond, then it is given the E designation.
E isomer
(E)-1-bromo-2-chloro-2-fluoro-1-iodoethene
Substituted cyclic compounds can also have cis and trans isomers depending on whether
the substituents are attached on the same or opposite faces of the ring.
(cis-1,4-dichlorocyclohexane)
(trans-1,4-dichlorocyclohexane)
The above compounds can also be represented as follows:
They could also be represented using the chair conformation. The chair conformers that
are equivalent to the above structural formula are:
The stability of the compounds depends on the position of the substituents. Substituents
located at the equatorial position would be pointing away from the ring and will not
interact with the other atoms attached to the ring. This will make the compound more
stable. When the substituents are attached to the axial position, they can interact with the
other atoms in the ring (1, 3 diaxial interactions) and this will make the compound less
stable.