1. stereoisomerism 2. chirality 3. naming stereocenters - r/s configuration 4. acyclic molecules...
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1. Stereoisomerism2. Chirality 3. Naming stereocenters - R/S configuration4. Acyclic Molecules with 2 or more stereocenters5. Cyclic Molecules with 2 or more stereocenters6. Properties of Stereocenters7. Optical activity8. Separation of Enantiomers, Resolution9. Significance of Chirality in the biological world
StereochemistryStereochemistryOH
CH
H3C F
HO
CH
H3CF
20
Chapter 3
a b c
enantiomersmirror images
non-superposable
diastereomersnon-mirror images(cis/trans)
ISOMERISMsame molecular formula, but different….
conformational isomerschair/boat
configurational isomers
stereoisomers - same connectivitydifferent 3D orientation
constitutionalconnectivity
different
diastereomers
H
BrCl
H
H
BrH
Cl
trans cis
ClBr
HHCl
H
BrH
F3C
OC
CC
H
NH
CH3H H
H H
CC
C
H
NH
CH3H H
H HF3C
O
e.g. Prozac - one isomer (“S”) is significantly more active
enantiomers
- right and left-handed substances - 2 spatial arrangements of atoms- analyze reflections (mirrors)
same (achiral), different (chiral).
plane
chiral -non-superposable, different arrangements in space
mirror
Chirality
Elements of Elements of SymmetrySymmetry
Plane of symmetry: an imaginary plane passing through an object dividing it such that one half is the mirror image of the other half.
anti - point of symmetry
CH3
CHO H
H3C
OHHC
syn - plane of symmetry
CH3
CHO H
CH3
CHO H
Elements of SymmetryElements of SymmetryConformations of 2,3-butanediol*
.
If symmetry element is present, substance is achiral
.
*meso or R,S (later)
Elements of Elements of SymmetrySymmetry
Center of symmetry: a point situated so identical components of the object are located equidistant on opposite sides.
FBr
F Br
superposable mirror images - same compound - a plane of symmetry - achiral
rotate 180o
Chirality
Different, non-superposable mirror images, enantiomers
Chirality-sp3 or tetrahedral center with 4 different groups = chiral molecule
Cl
CF
BrH
Cl
CF
BrH rotate e.g. (180o)
see if images aresuperposable, e.g.
Cl
CF
HBr
Tetrahedral - 4 different substituents (sp3)
Cl
CF
BrH
Cl
CF
BrH
enantiomers
StereocenterStereogenic center
- an atom that interchange of 2 groups gives a stereoisomer
EnantiomersEnantiomers
Lactic acidC
CO2H
HH3CHO
C
HO2C
HCH3OH
How do we distinguish chiral molecules?
R/SR S
Priority rules
1. Assign priority to each atom bonded to stereocenter.
higher atomic number
higher priority
R,S ConventionR,S Convention
(1) (6)
-CH3-H
Increasing priority
(7)
-NH2
(8)
-OH(17)
-Cl(35)
-Br(0)
2. If same atoms bonded to the stereocenter, look to next set of atoms.
Priority to the first point of difference.
R,S ConventionR,S Convention
Z
CH3
CH2CH3
CH2NH2
HOH2C
“Z” stereocenter, 4 gps.
Z
C
CH2CH3
CH2NH2
HOH2C
HH
H(1)
Z
C
C-CH3
CH2NH2
HOH2C
HH
H(1)
H
H
(6)Z
C
C-CH3
C
HOH2C
HH
H(1)
H
H
(6)
(7)H
HNH2
Z
C
C-CH3
C
C
HH
H(1)
H
H
(6)
(7)
(8)
HH
NH2
H
H
H-O O > N > C > H
8 > 7 > 6 > 1
R/S absolute configuration of chiral compoundsRules:
1. Identify stereogenic center (C - 4 different gps.)2. Assign priority to groups (C - 1, 2, 3, 4)
3
C
2 1
4
3. View C with “4” back; 1, 2, 3 FRONT
2
3
1
4C
4. If 1>2>3 clockwise = R; counterclockwise = S
R
enantiomers
R & S configuration
OH
Cl
OH
Cl
O Cl
H
OCl
H
R S
3. Atoms in double (triple) bond viewed as equivalent number of single bonds
(C is a stereogenic center)
R,S ConventionR,S Convention
CC
C
H
F
C H
C
C
H
H H
H HH
H
HH
C
CH
CHH
view asC
C
H
C
C
CH H
CC
C
H
F
C H
C
C
H
H H
H HH
H
HH
CC
H
C
vs
C
C
H
C
H H
H
H
H H
C
C
HC
C
H
C
CHH
1
4
2
3
vs
C
H
C
C
CH
H
S
priorities and assigning R/S
O
O
HF
O
Assign R/S to the stereogenic center of the ester
rotate 180o
S
O
O
FH
O
Assign R or S to carvone O
H
spearmint
S caraway/dill
R
N
H
H
Assign R/S to stereogenic carbon in coniine
Golden pitcher plant
R-(-)-coniine poison hemlock
For a molecule with n stereocenters, a maximum of 2n
stereoisomers “might” be possible.
Enantiomers & DiastereomersEnantiomers & Diastereomers
For a molecule with 1 stereocenter, 21 = 2 stereoisomers are possible.
For a molecule with 2 stereocenters, a MAXIMUM of 22 = 4 stereoisomers might exist.
O
O
OH
H
H
H
(sugar-O)3
256 (ignore sugar)
2n
O
O
HF
O
R|S
earlier
SR
R - RR - SS - RS - S
O
O
HF
O
H
what about a second center?
Cl
BrMolecules with more than 1 stereocenter
22 = 4trans-1-bromo-2-chlorocyclopropane**
relative stereochemistry - both are ‘trans’
absolute stereochemistry - each is unique, enantiomers
Cl
H
H
H
H
Br
Cl
H
H
H
H
Br
RR S S
(1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane
Molecules with more than 1 stereocenter
trans-1-bromo-2-chlorocyclopropane
Cl
H
H
H
Br
H
Cl
H
H
H
Br
H
R S SR
cis-1-bromo-2-chlorocyclopropane Cl
Br
**
22 = 4
Cl
H
H
H
H
Br
Cl
H
H
H
H
Br
RR S S
(1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane
(1S,2R)-1-bromo-2-chlorocyclopropane (1R,2S)-1-bromo-2-chlorocyclopropane
Molecules with more than 1 stereocenter
Cl
H
H
H
Br
H
Cl
H
H
H
Br
H
R S SR
Cl
H
H
H
H
Br
Cl
H
H
H
H
Br
RR S S
(1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane
(1S,2R)-1-bromo-2-chlorocyclopropane (1R,2S)-1-bromo-2-chlorocyclopropane
Molecules with more than 1 stereocenter
R S SR
RR S S
(1R,2R)-1-bromo-2-chlorocyclopropane (1S,2S)-1-bromo-2-chlorocyclopropane
(1S,2R)-1-bromo-2-chlorocyclopropane (1R,2S)-1-bromo-2-chlorocyclopropane
Cl BrHH Br Cl
HH
Cl H
BrHH Cl
HBr
CH3
Br
H
Br
H
C CH3C
H3C
H
Br
Br
H
CCCH3 CH3
H
Br
Br
H
C CH3C
2 or more stereocenters with symmetry leads to a meso isomer, superposable mirror images.
Consider 2,3-dibromobutane:
S S
H3C
Br
H
Br
H
CCCH3
S S RR
RR
CH3
Br
H
Br
H
C CH3CCH3
Br
H
Br
H
C CH3C CH3
Br
H
Br
H
C CH3C
2 or more stereocenters with symmetry leads to a meso isomer, superposable mirror images.
Consider 2,3-dibromobutane:
only 3 realized
H3C
H
Br
Br
H
CCCH3 CH3
H
Br
Br
H
C CH3C
H3C
Br
H
Br
H
CCCH3 CH3
Br
H
Br
H
C CH3C
S S R R
S SR R
meso isomer is diastereomeric to enantiomers
meso isomer
part2