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Stereochemistry: Chiral Molecules
Chapter 5
Constitutional Isomers = same molecular formula, different
connectivity Stereoisomers = same molecular formula, same connectivity
of atoms but different arrangement of atoms in space
Isomerism: Constitutional Isomers and Stereoisomers
Examples of Constitutional Isomers
formula
constitutional isomers
C
H 3
O 8
CH
CH 3
CH 2
OH 2
CH
CHCH 3
3
C
H 4
10
CH
CH 3
CH 2
CH 2
3
CH
CHCH 3
3
OH CH
3
Constitutional Isomers - Review
Same molecular formula – different bond connectivitiesAlways different propertiesVery different properties if different functional groups
Stereochemistry
Although everything has a mirror image, mirror imagesmay or may not be superimposable.
Some molecules are like hands. Left and right hands aremirror images, but they are not identical, orsuperimposable.
Chiral and Achiral Molecules
Stereochemistry
•^
Other molecules are likesocks. Two socks from a pairare mirror images that aresuperimposable. A sock andits mirror image are identical.
-^
A molecule or object that issuperimposable on its mirrorimage is said to be achiral.
Chiral and Achiral Molecules
Stereochemistry
We can now consider several molecules to determinewhether or not they are chiral.
Chiral and Achiral Molecules
Mirror image = converts right hand into left
Stereochemistry
The molecule labeled A and its mirror image labeled Bare not superimposable. No matter how you rotate A andB, all the atoms never align. Thus, CHBrClF is a chiralmolecule, and A and B are different compounds.
A and B are stereoisomers—specifically, they areenantiomers. - A carbon atom with four different groups is a tetrahedralstereogenic center.
Chiral and Achiral Molecules
Stereochemistry
Larger organic molecules can have two, three or evenhundreds of stereogenic centers.
Stereogenic Centers
Stereochemistry
Stereogenic centers may also occur at carbon atomsthat are part of a ring.
To find stereogenic centers on ring carbons, alwaysdraw the rings as flat polygons, and look for tetrahedralcarbons that are bonded to four different groups.
Stereogenic Centers
Stereochemistry
In 3-methylcyclohexene, the CH
3
and H substituents that
are above and below the plane of the ring are drawn withwedges and dashes as usual.
Stereogenic Centers
Stereochemistry
Stereogenic Centers •^
Manybiologicallyactivemoleculescontainstereogeniccenters onring carbons.
Enantiomers: stereoisomers whose molecules arenonsuperposable mirror images
Diastereomers: stereoisomers whose molecules are notmirror images of each other
Î
Example: cis and trans double bond isomers Î
Example: cis and trans cycloalkane isomers
Two types of stereoisomers
Chiral molecule - has the property of handedness^ z
Not superimposable on its mirror image z
Can exist as a pair of enantiomers
Pair of enantiomers^ z
A chiral molecule and its mirror image
Achiral molecule^ z
Superimposable on its mirror image
Enantiomers and Chiral Molecules
A molecule with a single tetrahedral carbon bonded to fourdifferent groups will always be chiral
Switching two groups at the tetrahedral center leads to theenantiomeric molecule
A molecule with more than one tetrahedral carbon bonded tofour different groups is not always chiral]- LATERStereogenic Center (also called a “stereocenter”)^ Î
In general it is “an atom bearing groups of such nature that aninterchange of any two groups will produce a stereoisomer” Î
sp
3 carbon is the most common example of a tetrahedral stereogenic center. They are usually designated with an asterisk (*)
z
Example: 2-butanol
Chiral molecules and stereogenic centers
Mirror images not superimposable = enantiomers
Stereochemistry
Since enantiomers are two different compounds, theyneed to be distinguished by name. This is done byadding the prefix
R
or
S
to the IUPAC name of the
enantiomer.
Naming enantiomers with the prefixes
R
or
S
is called
the Cahn-Ingold-Prelog system.
To designate enantiomers as
R
or
S
, priorities must be
assigned to each group bonded to the stereogeniccenter, in order of decreasing atomic number. The atomof highest atomic number gets the highest priority (1).
Labeling Stereogenic Centers with
R
or
S
Stereochemistry
If two atoms on a stereogenic center are the same,assign priority based on the atomic number of the atomsbonded to these atoms. One atom of higher prioritydetermines the higher priority.
Labeling Stereogenic Centers with
R
or
S
Stereochemistry
•^
To assign a priority to an atom that is part of a multiple bond,treat a multiply bonded atom as an equivalent number ofsingly bonded atoms. For example, the C of a C=O isconsidered to be bonded to two O atoms. Labeling Stereogenic Centers with
R
or
S
•^
Other common multiple bonds are drawn below:
Stereochemistry
Labeling Stereogenic Centers with
R
or
S
Stereochemistry
Labeling Stereogenic Centers with
R
or
S
Stereochemistry
Labeling Stereogenic Centers with
R
or
S
Stereochemistry
Labeling Stereogenic Centers with
R
or
S
Stereochemistry
Labeling Stereogenic Centers with
R
or
S
Plane polarized light oscillates in a single plane
Like a rope through a picket
fence
The plane-polarized light cannot get throughTwo filters that are 90
˚^ to one another.
Schematic of a Polarimeter
Stereochemistry
With achiral compounds, the light that exits the sampletube remains unchanged. A compound that does notchange the plane of polarized light is said to be opticallyinactive.
Physical Properties of Stereoisomers
Stereochemistry
With chiral compounds, the plane of the polarized light isrotated through an angle
α
. The angle
α
is measured in
degrees (
0 ), and is called the observed rotation. A
compound that rotates polarized light is said to be opticallyactive.
Physical Properties of Stereoisomers
Stereochemistry
The rotation of polarized light can be clockwise oranticlockwise.
If the rotation is clockwise (to the right of the noonposition), the compound is called dextrorotatory. Therotation is labeled
d
or (+).
If the rotation is counterclockwise, (to the left of noon),the compound is called levorotatory. The rotation islabeled
l
or (-).
Two enantiomers rotate plane-polarized light to an equalextent but in opposite directions. Thus, if enantiomer Arotates polarized light +
0 , the same concentration of
enantiomer B rotates it –
0
No relationship exists between
R
and
S
prefixes and the
(+) and (-) designations that indicate optical rotation.
Physical Properties of Stereoisomers
Stereochemistry
An equal amount of two enantiomers is called a racemicmixture or a racemate. A racemic mixture is opticallyinactive. Because two enantiomers rotate plane-polarized light to an equal extent but in oppositedirections, the rotations cancel, and no rotation isobserved.
Physical Properties of Stereoisomers
No net optical rotation
Often designated as (
Racemic mixture = racemate
Racemic Mixture = A 1:1 mixture of enantiomers
Equal amountsof each
Stereochemistry
Specific rotation is a standardized physical constant forthe amount that a chiral compound rotates plane-polarized light. Specific rotation is denoted by thesymbol [
α
] and defined using a specific sample tube
length (
l , in dm), concentration (
c
in g/mL), temperature
(^0) C) and wavelength (589 nm).
Physical Properties of Stereoisomers
Chiral Drugs and Pharmaceutical Companies
Typically only one enantiomer of a drug is biologically active
Ibuprofen (active)
(inactive)
(S)
(R)
HO
CH
3
H O
HO
H
CH
(^3) O
Stereochemistry
Chemical Properties of Enantiomers
Molecules with More than One Stereogenic Center
Each new stereogenic center may generate a potential pair ofstereoisomers, so the theoretical number of possible stereoisomersis 2
n
How many stereoisomers?
Relationship of 1 and 2 = enantiomersRelationship of 3 and 4 = enantiomers
(Enantiomers = same properties, cannot be separated)
Relationship of (1 and 3), (2 and 3), or (1 and 4) = diastereomers
z
Diastereomers: stereoisomers that are not mirror images ofeach other.They have
different physical properties
and can be separated
Four stereoisomers of 2,3-dibromopentane
Four stereoisomers of 2,3-dibromopentane
Let’s figure out the configurations of all 4 stereoisomers
CH
3 C
H
Br
C CH
CH 2
3
H
Br
CH
3 C
H
Br
C CH
CH 2
H^3
Br
CH
3 C
Br
H
C CH
CH 2
3
H
Br
CH
3 C
H
Br
C CH
CH 2
3
Br
H
S R Use the same rules, and assign eachstereogenic center separately
Stereochemistry
When a compound has more than one stereogeniccenter, the
R
and
S
configuration must be assigned to
each of them.
R
and
S
Assignments in Compounds with Two or
More Stereogenic Centers.
One stereoisomer of 2,3-dibromopentane
The complete name is (
S ,
R
)-2,3-dibromopentane
Sometimes molecules with 2 or more stereogenic centerswill have fewer than 2
n^
stereoisomers
Meso compounds
Because superposable on its mirror image
Despite the presence of stereogenic centers
Not optically active
Has a plane of symmetry
Meso compound are achiral
Definition: a meso compound is a compound that is
achiral despite having stereogenic centers
Stereochemistry
•^
To draw the other two stereoisomers if they exist, draw mirrorimages of each compound and determine whether thecompound and its mirror image are superimposable.
Disubstituted Cycloalkanes^ •
The
cis
isomer is superimposable on its mirror image, making
the images identical. Thus, A is an achiral meso compound.
Stereochemistry
•^
The trans isomer is not superimposable on its mirror image,labeled C, making B and C different compounds. B and C areenantiomers.
Disubstituted Cycloalkanes^ •
Because one stereoisomer of 1,3-dibromocyclopentane issuperimposable on its mirror image, there are only threestereoisomers, not four.
z
1,4-dimethylcyclohexane
Î
Neither the cis not trans isomers is optically active Î
Stereoisomerism of Cyclic Compounds Each has a plane of symmetry
1,3-dimethylcyclohexane z
The trans and cis compounds each have twostereogenic centers z
The cis compound has a plane of symmetry and is
meso
z
The trans compound exists as a pair of enantiomers Ring flip of (
a)
produces another
(a),
not the mirror image (
b)
No plane of symmetry
Me Me H
H
plane
of sym
metry
Racemic Form (identical properties)
R S
reaction
R
+
Diastereomers (different properties)
R
R S
R
separate
R
R S
R
- -
R R
pure forms
R S
Separation of enantiomers = resolution
Cannot be separated directly Why not?Can be separated by a chiral reagent which creates diastereomeric relationship
is a resolving agent. It is
a single enantiomer
of a chiral compound
that can react with
both enantiomers of the racemic mixture toform a pair of diastereomers.
R
quinine
(primary alkaloid from variousspecies of
Cinchona
)
N
HO H
N
H
CH
O 3
General Approach to Resolution
Often used are organic acids or bases which are found optically pure innatureThey form acid-base salts which, as diastereomers, have differentsolubilities in water and can be separated by selective crystallizationOne can then easily regenerate starting acid or base
(+,-)-2-phenylpropanoic acid
(racemic form)
C
H 6
CCOOH 5 CH
3 H
+
(-)-alkaloid
(+)(-)-Salt(-)(-)-Salt diastereomers
(basic)
separate byfractionalcrystallization
(+)(-)-Salt
(-)(-)-Salt
organic phase
water phase
(+)-
(-)-alkaloid asammonium salt
organic phase
water phase
(-)-
(-)-alkaloid asammonium salt
H
O 3
+
C
H 6
CHCCOOH 5
3 H
H
O 3
+
C
H 6
CCOOH 5 CH
3 H
Resolution of a Carboxylic Acid
