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Chapter 6. Isomers and Stereochemistry
Learning objectives:
1. Differentiate chiral and achiral molecules.
2. Recognize and draw structural isomers (constitutional isomers), stereoisomers
including enantiomers and diastereomers, racemic mixture, and meso compounds.
3. Identify the stereocenters in a molecule and assign the configuration as R or S.
4. Know the relationship between enantiomers and their specific rotations.
Sections to be covered (in the order of delivery):
6.1 Stereoisomers
6.2 Chiral Molecules
6.3 Enantiomers and Diastereomers
6.4 Properties of Chiral Molecules
6.1 Stereoisomers
Important Terminologies: achiral, chiral, plane of symmetry, mirror image and
superimposable
A. Classification of Isomers
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Examples:
B. Cis-trans (E/Z) Isomers are Diastereomers of Restricted C-C Bond Rotation
CH3
CH3
CH3
CH3
CH3
CH3
I II III
H
H3C H
CH3 H
H CH3
CH3
IV V
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C. A chiral object has a nonsuperimposable mirror image
D. Drawing Mirror Image (Enantiomers)
Examples:
OH
Br
CH3CH2
H
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E. Self-assessment Questions
Can you identify stereoisomer and same molecule using mirror image?
Can you draw the mirror image of a given compound?
Can you describe the definition of structural isomer, conformer (conformational
isomer), stereoisomer, enantiomer and diastereomer?
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6.2 Chiral Molecules
Chiral molecules: molecules without plane of symmetry!
Enantiomers: chiral molecules that are mirror image to each other
Diastereomers: chiral molecules that are not mirror image to each other
A. Criteria of Being Chiral Molecule
Know stereocenter (chiral center, chiral atom)
(i) Universal definition
Not superimposable with its mirror image.
or
No plane of symmetry.
(ii) Simplified criteria but may have exception
The presence of stereocenter (chiral center, chiral atom): four different
substituents for an sp3 hybridized atom.
Chiral molecules may have no stereocenter.
Having sterocenters may not be chiral.
(iii) Stereocenter and chiral center (chiral atom)
B. Find Plane of Symmetry
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C. Stereocenters (chiral atoms)
For molecules that are hard to find plane of symmetry, find stereocenter (atom).
sp3 hybridized C and N
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S and P
Examples:
D. Identify Chiral Molecules Using Stereocenter
(i) Molecules with odd number of stereocenters:
(ii) Molecules with even number of stereocenters:
Look for plane of symmetry or assign R and S
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(i) Useful for molecules that have multiple stereocenters
(ii) How to Assign R and S for Stereocenters?
1. Prioritize (atomic number) four substituents (groups) attached to a stereocenter.
2. Place the less prioritized one (4) away from you and then rotate from 1-2-3.
Examples:
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F. Self-assessment Questions
Can you identify stereoisomer(s)?
Can you explain the relationship among stereocenter, chiral molecule,
enantiomer and diastereomer?
Can you assign R and S of stereocenter (atom)?
Can you explain what are racemic mixture and meso compound?
6.3 Enantiomers and Diastereomers
Know the difference between enantiomers and diastereomers
Mirror image to each other: enantiomers
Not mirror image to each other: diastereomers (commonly have multiple
stereocenters)
Both enentiomers and diastereomers are stereoisomers
Example:
Threonine
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A. Assign R and S for identification:
Enantiomers:
Diastereomers:
B. Racemic Mixtures: a pair of enantiomers in 1/1 ratio
Optical property is canceled intermolecularly.
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C. Meso Compounds (the presence of plane of symmetry)
Meso compounds have asymmetric centers but are optically inactive
Optical property is canceled intramolecularly.
C
C
OH
HO
O
HO
OH
O
HO2C
CO2H
HO
OH
(i) Assign R and S for identification and check the presence of plane of symmetry:
D. More examples Racemic Mixture and Meso Compounds
(i)
HO2C
CH3
HO
OH
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(ii)
I II III IV
OH
CH3
OH
CH3
OH
CH3
OH
CH3
CH3
CH3
V
(iii)
CH3
OH
CH3
OH CH3
OH
H3COH
I II IIIIV
V
OH
CH3
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E. Molecules with Three or More Stereocenters
OH
OH
Menthol
Number of possible stereoisomers: 2n, n = number of stereocenters
HOHO
H
H H
H
F. Self-assessment Questions
Can you identify a pair of enantiomers and diastereomers?
Can you explain racemic mixture and meso compound?
Can you calculate the possible stereoisomers for molecules with three or more
stereocenters?
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6.4 Properties of Chiral Molecules
Important Terminologies: plane-polarized light, optically active, optical activity.
A. Plane-Polarized Light
B. A Polarimeter
Specific rotation: the observed rotation of an optically active substance at a
concentration of 1 g/100 mL in a sample tube 10 cm long;
for a pure liquid, concentration is in g/mL (density)
C. Chiral compounds with clockwise rotation is designated as (+).Chiral compounds
with counterclockwise rotation is designated as (-).
(+) and (-) have no correlation with R and S assignment.
Light source
Light filter with grid
Sample tube with chiral compound
Rotatable filter with grid
1
2
3
4
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D. Racemic Mixture and Meso Compounds Are Optically Inactive
E. Properties of stereoisomers
Enantiomers: same chemical properties (reactivity), same physical properties
(ex. boiling point, melting point, density and pKa) except for the
specific rotation (a pair of Enantiomers has the exact opposite
direction in rotation).
Diastereomers: different chemical and physical properties.
(i) Separation of Enantiomers: Resolution
[R]
[S]
[R]
[R]
[R][R]
[R][S]
[S][S]
[S]
[S]
Addition of optically pure
reagent
[R*]
[R,R*]
a racemic mixture
a pair of enantiomers ([R] and [S])
[R,R*]
[R,R*]
[R,R*]
[R,R*]
[S,R*]
[S,R*] [S,R*]
[S,R*]
[S,R*]
a mixture of diastereomers ([R,R*] and [S,R*])
separation of diastereomers
[R,R*]
[S,R*]
Removal of optically pure
reagent
Removal of optically pure
reagent
[R*]
[R*]
[S] [S]
[S]
[S] [S]
[R][R]
[R]
[R] [R]
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(ii) The Significance of Chirality in the Biological World
HO2C
H3C H
HO2C
H3C H
OCH3 (S)-Ibuprofen (S)-Naproxen
F. Stereoselectivity: Selection Between Stereoisomers
(i) reactions for alkenes
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(ii) The stereochemistry of enzyme-catalyzed reactions
C
C H
CO2-
CO2-
H
HHOC
C
-O2C
CO2-
+ H2O
H
H
fumurate
fumarase
malate
G. Self-assessment Questions
Do you know the relationship of chemical and physical properties between a pair
of enantiomers and diastereomers?
Can you explain why racemic mixture and meso compound are optically inactive?
Can you explain the process of separating a pair of enantiomers (resolution)?
Can you identify a stereoselective reaction?