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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
6.2
6.3
6.4
Stereoisomers
Chiral Molecules
Enantiomers and Diastereomers
Properties of Chiral Molecules
6.1
Stereoisomers
Important Terminologies: achiral, chiral, plane of symmetry, mirror image and
superimposable
A. Classification of Isomers
1
Examples:
B. Cis-trans (E/Z) Isomers are Diastereomers of Restricted C-C Bond Rotation
CH3
CH3
CH3
CH3
CH3
CH3
I
II
H
H3C
III
CH3
H
CH3
H
H
CH3
IV
V
2
C. A chiral object has a nonsuperimposable mirror image
D. Drawing Mirror Image (Enantiomers)
Examples:
OH
Br
CH3CH2
H
3
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?
4
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
5
C. Stereocenters (chiral atoms)
For molecules that are hard to find plane of symmetry, find stereocenter (atom).
sp3 hybridized C and N
6
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
7
E. Assign R and S for Stereocenters
Know racemic mixture and meso compounds
8
(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:
9
10
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
11
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.
12
C. Meso Compounds (the presence of plane of symmetry)
Meso compounds have asymmetric centers but are optically inactive
Optical property is canceled intramolecularly.
OH
OH
O
C
HO2C
OH
HO
CO2H
C
HO
HO
O
(i) Assign R and S for identification and check the presence of plane of symmetry:
D. More examples Racemic Mixture and Meso Compounds
(i)
OH
HO2C
CH3
HO
13
(ii)
CH3
CH3
CH3
CH3
CH3
OH
OH
OH
OH
CH3
II
I
III
V
IV
(iii)
OH
OH
OH
OH
CH3
I
H3C
CH3
CH3
III
II
IV
OH
CH3
V
14
E. Molecules with Three or More Stereocenters
OH
OH
Menthol
Number of possible stereoisomers: 2n, n = number of stereocenters
H
H
H
H
HO
HO
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?
15
6.4 Properties of Chiral Molecules
Important Terminologies: plane-polarized light, optically active, optical activity.
A. Plane-Polarized Light
B. A Polarimeter
Light source
1
Light filter with grid
2
Sample tube
with chiral
compound 3
Rotatable filter
with grid
4
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.
16
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,R*]
[R]
[R] [S]
[S]
[R]
[R]
[S] [S]
[R]
[S]
[R]
[S]
a racemic mixture
a pair of enantiomers
([R] and [S])
Addition of
optically pure
reagent
[R*]
Removal of
optically pure
reagent
[S,R*]
[R,R*]
[R,R*]
[R,R*]
[S,R*]
[S,R*]
separation of
diastereomers
[R,R*]
[S,R*]
[R,R*]
[S,R*]
[S,R*]
[R*]
Removal of
optically pure
reagent
a mixture of diastereomers
([R,R*] and [S,R*])
[S]
[S]
[S]
[S]
[S]
[R*]
17
[R]
[R]
[R]
[R]
[R]
(ii) The Significance of Chirality in the Biological World
H3C
H3C
H
H
HO2C
HO2C
OCH3
(S)-Ibuprofen
(S)-Naproxen
F. Stereoselectivity: Selection Between Stereoisomers
(i) reactions for alkenes
18
(ii) The stereochemistry of enzyme-catalyzed reactions
CO2-
CO2-
H
C
+ H2O
fumarase
C
-
O 2C
HO
H
H
fumurate
C
H
C
H
CO2-
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?
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