chapter 6. isomers and stereochemistry learning...
TRANSCRIPT
1
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 Cis-trans isomers result from restricted rotation 6.2 A chiral object has a nonsuperimposable mirror image 6.3 An asymmetric center is the cause of chirality in a molecule 6.4 Isomers with one asymmetric center 6.5 How to draw enantiomers 6.6 Naming enantiomers by the R,S system 6.7 Chiral compounds are optically active 6.8 How specific rotation is measured 6.9 Isomers with more than one asymmetric center 6.10 Meso compounds have asymmetric centers but are optically inactive 6.11 How enantiomers can be separated 6.12 Receptors 6.13 The stereochemistry of reactions 6.14 The stereochemistry of enzyme-catalyzed reactions # Sections that will be skipped Recommended additional problems 30, 32, 34, 35, 36, 42, 49, 55
2
6.1 Cis-trans isomers result from restricted rotation Alkenes and cycloalkanes
CH3
CH3
CH3
CH3
CH3
CH3
I II III
H
H3C H
CH3 H
H CH3
CH3
IV V 6.2 A chiral object has a nonsuperimposable mirror image
3
6.3 An asymmetric center is the cause of chirality in a molecule 6.4 Isomers with one asymmetric center 6.5 How to draw enantiomers A. What Are Enantiomers?
Isomers
Constitutional Isomer Stereoisomer (Structural Isomer)
Enantiomer Diastereomer Enantiomers (a pair of enantiomers): mirror image but not superimposable
Br
CH3CH2 CH3
H
4
Important Terminologies: achiral, chiral, plane of symmetry, mirror image and stereocenter B. Drawing Enantiomers: Criteria of being chiral: four different substituents (SP3 hybridization) and no plane of symmetry. Examples:
OH
Br
CH3CH2H
5
6.6 Naming enantiomers by the R,S system (i) Locate the stereocenter and prioritize its four substitutents from 1 (highest) to 4 (lowest). (ii) Rotate in the order from 1 to 2 to 3. (iii) If the 4 (lowest) substituent is pointing away from you, clockwise rotation will be R and counterclockwise rotation will be S. (iv) If the 4 (lowest) substituent is pointing toward you, clockwise rotation will be S and counterclockwise rotation will be R. (v) Examples
Cl
OH
OH
C
Cl
O
H
CH3HO2CCl
6
6.7 Chiral compounds are optically active 6.8 How specific rotation is measured 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
7
6.9 Isomers with more than one asymmetric center
Know the difference between enantiomers and diastereomers
C OH
OH
O
H
OH
A. Assign R and S for identification:
H
CHO
OH
OH
CH2OH
H
HO
CHO
H
H
CH2OH
HO
I II
H
CHO
OH
H
CH2OH
HO
HO
CHO
H
OH
CH2OH
H
III IV
Enantiomers: Diastereomers: B. Racemic Mixtures: a pair of enantiomers in 1/1 ratio Optical property is canceled intermolecularly.
8
6.10 Meso compounds have asymmetric centers but are optically inactive Meso Compounds (the presence of plane of symmetry) Optical property is canceled intramolecularly.
CC
OH
HO
O
HO
OH
O
HO2CCO2H
HO
OH
A. Assign R and S for identification and check the presence of plane of symmetry:
H
CO2H
OH
OH
CO2H
H
HO
CO2H
H
H
CO2H
HO
I II
H
CO2H
OH
H
CO2H
HO
HO
CO2H
H
OH
CO2H
H
III IV
B. More examples: (i)
HO2CCH3
HO
OH
(ii)
HO2CCO2H
HO
Br
9
(iii)
I II III IV
OH
CH3
OH
CH3
OH
CH3
OH
CH3
CH3
CH3
V
(iv)
CH3
OH
CH3
OH CH3
OH
H3COH
I II III IV
V
OH
CH3
10
C. Molecules with three or ore stereocenters
OH
OH
Menthol Number of possible stereoisomers: 2n, n = number of stereocenters
HOHO
H
H H
H
6.11 How enantiomers can be separated A. 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.
11
B. 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]
6.12 Receptors The Significance of Chirality in the Biological World
HO2C
H3C H
HO2C
H3C H
OCH3 (S)-Ibuprofen (S)-Naproxen
12
6.13 The stereochemistry of reactions 6.14 The stereochemistry of enzyme-catalyzed reactions
C
C H
CO2-
CO2-
H
HHOC
C
-O2C
CO2-
+ H2O
H
H
fumurate
fumarase
malate