7 stereochem
TRANSCRIPT
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Stereochemistry
&Chiral Molecules
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Stereochemistry
stereochemistry is the three-dimensional structure of a
molecule.
As a consequence of stereochemistry, apparently minor
differences in 3-D structure can result in vastly different
properties. We can observe this by considering starch and
cellulose, which are both composed of the same repeating
unit.
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Stereochemistry of Carbohydrates
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isomers are different compounds with the samemolecular formula.
The two major classes of isomers are constitutional
isomers and stereoisomers.
Constitutional isomers have different IUPAC names,
the same or different functional groups, different
physical properties and different chemical properties.
Stereoisomers differ only in the way the atoms areoriented in space. They have identical IUPAC names
(except for a prefix like cis ortrans and E or Z). They
always have the same functional group.
Two Major Classes of Isomers
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Configurational Isomers
Configurational isomers have a particular three-
dimensional arrangement of atoms called a
configuration.
Configuration is the spatial array of atoms that
distinguishes stereoisomers.
Configurational isomers are stereoisomers that
differ in configuration.
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Constitutional Isomers vs Stereoisomers
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Although everything has a mirror image, mirror imagesmay or may not be superimposable.
Some molecules are like hands. Left and right hands are
mirror images, but they are not identical, or
superimposable.
Chirality or Handedness
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Other molecules are like
socks. Two socks from a pair
are mirror images that are
superimposable. A sock and
its mirror image are identical.
A molecule or object that is
superimposable on its mirror
image is said to be achiral.
Achiral Objects and Molecules
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Do these molecules conatain a Plane of Symmetry (Mirror Plane)?
Achiral Molecules
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The molecule labeled A and its mirror image labeled B
are not superimposable. No matter how you rotate A and
B, all the atoms never align. Thus, CHBrClF is a chiral
molecule, and A and B are different compounds.
A and B are stereoisomersspecifically, they are
enantiomers. A carbon atom with four different groups is a tetrahedral
stereogenic center.
Chiral Molecules
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In general, a molecule with no stereogenic centers willnot be chiral. There are exceptions to this that will be
considered in Chapter 17.
With one stereogenic center, a molecule will always be
chiral.
With two or more stereogenic centers, a molecule may or
may not be chiral, e.g. Meso compound (contains a plane
of symmetry or a mirror plane)
Achiral molecules contain a plane of symmetry but chiral
molecules do not. A plane of symmetry is a mirror plane that cuts the
molecule in half, so that one half of the molecule is a
reflection of the other half.
Chiral vs Achiral
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Plane of Symmetry
or
Mirror Plane
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Chiral vs Achiral
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To locate a stereogenic center, examine the four
groupsnot the four atomsbonded to each tetrahedralcarbon atom in a molecule.
Omit from consideration all C atoms that cannot be
tetrahedral stereogenic centers. These include
Methylene and methyl units, i. e. CH2 and CH3 groups
respectively.
Any sp orsp2 hybridized Carbons, e.g. triple bonds,
and double bonds in alkenes (C=C) and carbonyls
(C=O).
Stereogenic Centers
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Larger organic molecules can have two, three or even
hundreds of stereogenic centers.
Number of Stereogenic Centers in a Molecule
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Enantiomers
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One of a pair of molecular species that
are mirror images of each other and
not superposable.
They are mirror-image stereoisomers.
Enantiomers
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To draw both enantiomers of a chiral compound such as2-butanol, use the typical convention for depicting a
tetrahedron: place two bonds in the plane, one in front of
the plane on a wedge, and one behind the plane on a
dash. Then, to form the first enantiomer, arbitrarily place
the four groupsH, OH, CH3 and CH2CH3on any bondto the stereogenic center. Then draw the mirror image.
Drawing Enantiomers
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Pairs ofEnantiomers
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Stereogenic centers may also occur at carbon atoms
that are part of a ring.
To find stereogenic centers on ring carbons, always
draw the rings as flat polygons, and look for tetrahedral
carbons that are bonded to four different groups.
Stereogenic Centers in a cyclic Alkane
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In 3-methylcyclohexene, the CH3 and H substituents thatare above and below the plane of the ring are drawn with
wedges and dashes as usual.
Enantiomers of 3-methylcyclohexene
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Enantiomers of Biomolecules
Manybiologically
active
molecules
contain
stereogeniccenters on
ring carbons.
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Polycyclic Ethers
How many stereogenic centers are in this
polycyclic ether structure?
O
O
O
O
HO
OHH
HH
Me
HH
H
H
H
H
O
H
O
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R/S Isomers
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Since enantiomers are two different compounds, theyneed to be distinguished by name. This is done by
adding the prefix RorS to the IUPAC name of the
enantiomer.
Naming enantiomers with the prefixes RorS is called
the Cahn-Ingold-Prelog system.
To designate enantiomers as RorS, priorities must be
assigned to each group bonded to the stereogenic
center, in order of decreasing atomic number. The atom
of highest atomic number gets the highest priority (1).
Labeling Stereogenic Centers with RorS
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If two atoms on a stereogenic center are the same,assign priority based on the atomic number of the atoms
bonded to these atoms. One atom of higher priority
determines the higher priority.
Priority Rules for Naming Enantiomers (R or S)
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If two isotopes are bonded to the stereogenic center,assign priorities in order of decreasing mass number.
Thus, in comparing the three isotopes of hydrogen, the
order of priorities is:
Priority of Isotopes on a Stereogenic Center
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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 is
considered to be bonded to two O atoms.
Priority Rules for Multiple Bonds in (R or S) Labeling
Other common multiple bonds are drawn below:
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Examples Assigning Priorities
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Cahn-Ingold-Prelog System for
Naming Enantiomers R or S
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RorSEnantiomers
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R-enantiomer (ClockwiseRotation)
S-enantiomer (CounterclockwiseRotation)
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Manipulation of Chiral Molecules
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Switching any two groups on a molecule with a
single stereogenic center, converts the
molecule into its enantiomer.
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Enantiomers have identical physical properties, exceptfor how they interact with plane-polarized light.
Plane-polarized (polarized) light is light that has an
electric vector that oscillates in a single plane. Plane-
polarized light arises from passing ordinary light
through a polarizer.
A polarimeteris an instrument that allows polarized light
to travel through a sample tube containing an organic
compound. It permits the measurement of the degree to
which an organic compound rotates plane-polarizedlight.
Physical Properties of Stereoisomers
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With achiral compounds, the light that exits the sampletube remains unchanged. A compound that does not
change the plane of polarized light is said to be optically
inactive.
Polarimeter
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With chiral compounds, the plane of the polarized light is
rotated through an angle E. The angle E is measured indegrees (0), and is called the observed rotation. A
compound that rotates polarized light is said to be optically
active.
Optically Active Compounds
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The rotation of polarized light can be clockwise or
anticlockwise.
If the rotation is clockwise (to the right of the noon
position), the compound is called dextrorotatory. The
rotation is labeled dor (+).
If the rotation is counterclockwise, (to the left of noon),the compound is called levorotatory. The rotation is
labeled lor (-).
Two enantiomers rotate plane-polarized light to an equal
extent but in opposite directions. Thus, if enantiomer A
rotates polarized light +50, the same concentration of
enantiomer B rotates it 50.
No relationship exists between Rand Sprefixes and the
(+) and (-) designations that indicate optical rotation.
Rotation of Polarized Light
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An equal amount of two enantiomers is called a
racemate or a racemic mixture. A racemic mixture is
optically inactive. Because two enantiomers rotate
plane-polarized light to an equal extent but in opposite
directions, the rotations cancel, and no rotation is
observed.
Racemates
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Specific rotation is a standardized physical constant forthe amount that a chiral compound rotates plane-
polarized light. Specific rotation is denoted by the
symbol [E] and defined using a specific sample tube
length (l, in dm), concentration (cin g/mL), temperature
(25 0C) and wavelength (589 nm).
Specific Rotation
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Enantiomeric excess (optical purity) is a measurement of
how much one enantiomer is present in excess of theracemic mixture. It is denoted by the symbol ee.
Optical Purity
ee = % of one enantiomer - % of the other enantiomer.
Calculating ee - If a mixture contains 75% of oneenantiomer and 25% of the other, the enantiomeric
excess is 75% - 25% = 50% ee.
50% ee means that there is a 50% excess of one
enantiomer over the racemic mixture.
The enantiomeric excess can also be calculated if the
specific rotation [E] of a mixture and the specific rotation
[E] of a pure enantiomer are known.
ee = ([E] mixture/[E] pure enantiomer) x 100.
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DiastereomersRelative Configuration
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For a molecule with n stereogenic centers, the maximumnumber of stereoisomers is 2n. Let us consider the stepwise
procedure for finding all the possible stereoisomers of 2,3-
dibromopentane.
Chiral Molecules with more than one
Stereocenter
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Diastereomers & Enantiomers
2,3-dibromopentane
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Let us now consider the stereoisomers of 2,3-dibromobutane.
Since this molecule has two stereogenic centers, the maximumnumber ofstereoisomers is 4.
Enantiomers of 2,3-dibromobutane
To find all the stereoisomers of 2,3-dibromobutane, arbitrarily
add the H, Br, and CH3 groups to the stereogenic centers,
forming one stereoisomer A, and then draw its mirror image, B.
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To find the other two stereoisomers if they exist, switch the
position of two groups on one stereogenic center of one
enantiomer only. In this case, switching the positions of H and Br
on one stereogenic center of A forms C, which is different from
both A and B.
Meso Compounds
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A meso compound is an achiral compound that containstetrahedral stereogenic centers. All meso compounds
contain a plane of symmetry.
Compound C has two stereogenic centers but it contains
a plane of symmetry, and is achiral; C is a meso
compound.
Meso Compounds
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The Three Stereoisomers of
2,3-dibromobutane
Because one stereoisomer of 2,3-dibromobutane is
superimposable on its mirror image, there are only three
stereoisomers, not four.
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When a compound has more than one stereogenic
center, the Rand Sconfiguration must be assigned to
each of them.
Rand SAssignments in Compounds with Two or More
Stereogenic Centers.
One stereoisomer of 2,3-dibromopentaneThe complete name is (2S,3R)-2,3-dibromopentane
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Since enantiomers have identical physical properties, they cannot
be separated by common physical techniques like distillation. Diastereomers and constitutional isomers have different physical
properties, and therefore can be separated by common physical
techniques.
Physical Properties of Stereoisomers
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Fischer projection formulas.
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Cis/Trans Isomers
Stereoisomers of Disubstituted
Cycloalkanes
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Cis/Trans 1,2-dimethylcyclopentanes
There are two different 1,2-dimethylcyclopentanesone having
two CH3 groups on the same side of the ring and one havingthem on opposite sides of the ring.
A and B are stereoisomers.
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Cis/trans Isomers
Stereoisomers are isomers that differ only in the way theatoms are oriented in space.
The prefixes cis and trans are used to distinguish these
isomers.
The cis isomerhas two groups on the same side of thering.
The trans isomerhas two groups on opposite sides of the
ring.
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Naming Rules for Disubstituted Cycloalkanes
Each of the cis and trans isomers of a disubstituted
cyclohexane, such as 1,4-dimethylcyclohexane, has twopossible chair conformations.
Cis and trans isomers are named by adding the prefixes cis
and trans to the name of the cycloalkane. Thus, the cis isomer
would be named cis-1,2-dimethylcyclopentane, and the trans
isomer would be named trans-1,2-dimethylcyclopentane.
All disubstituted cycloalkanes with two groups bonded to
different atoms have cis and trans isomers.
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Consider 1,3-dibromocyclopentane. Since it has two
stereogenic centers, it has a maximum of four stereoisomers.
Cis/Trans 1,3-disubstituted Cycloalkanes
Recall that a disubstituted cycloalkane can have two
substituents on the same side of the ring (cis isomer, A) or on
opposite sides of the ring (trans isomer, B). These
compounds are stereoisomers but not mirror images.
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To draw the other two stereoisomers if they exist, draw mirror
images of each compound and determine whether the
compound and its mirror image are superimposable.
cis-1,3-dibromocyclopentane
The cis isomer is superimposable on its mirror image, making
the images identical. Thus, A is an achiral meso compound.
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The trans isomer is not superimposable on its mirror image,
labeled C, making B and C different compounds. B and C areenantiomers.
trans-1,3-dibromocyclopentane
Because one stereoisomer of 1,3-dibromocyclopentane is
superimposable on its mirror image, there are only three
stereoisomers, not four.
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Skip problems 30, 31, 32, 61, 62 d,c
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Two enantiomers have exactly the same chemical properties except
for their reaction with chiral non-racemic reagents. Many drugs are chiral and often must react with a chiral receptor or
chiral enzyme to be effective. One enantiomer of a drug may
effectively treat a disease whereas its mirror image may be
ineffective or toxic.
Chemical Properties ofEnantiomers
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Chemical Properties ofEnantiomers
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Actually because of
priority rules a few are R,
but they all have thisconfiguration.
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Proteins
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