Organic Chemistry, 5th Edition
L. G. Wade, Jr.
Chapter 5
Stereochemistry
Jo Blackburn
Richland College, Dallas, TX
Dallas County Community College District
2003, Prentice Hall
Chirality
• “Handedness”: right glove doesn’t fit the
left hand.
• Mirror-image object is different from the
original object.
=>
Chapter 5
2
Stereoisomers
• Geometric isomers: cis-trans isomers.
• Enantiomers: nonsuperimposable mirror
images, different molecules.
=>
H
H
H
H
Cl
Cl
Cl
H
H
Cl
Cl
Cl
cis-1,2-dichlorocyclopentane
Cl
H
H
Cl
trans -1,2-dichlorocyclopentane
Chapter 5
3
Chiral Carbons
• Tetrahedral carbons with 4 different
attached groups are chiral.
• Its mirror image will be a different
compound (enantiomer).
=>
Chapter 5
4
Mirror Planes of Symmetry
• If two groups are
the same, carbon
is achiral.
(animation)
• A molecule with an
internal mirror
plane cannot be
chiral.*
Caution! If there is no plane of symmetry,
molecule may be chiral or achiral. See if
mirror image can be superimposed. =>
Chapter 5
5
(R), (S) Nomenclature
• Different molecules (enantiomers) must
have different names.
• Usually only one enantiomer will be
biologically active.
O
OH
C
• Configuration around the
chiral carbon is specified H3C C H
NH2
with (R) and (S).
natural alanine
Chapter 5
=>
6
Cahn-Ingold-Prelog Rules
• Assign a priority number to each group
attached to the chiral carbon.
• Atom with highest atomic number
assigned the highest priority #1.
• In case of ties, look at the next atoms
along the chain.
• Double and triple bonds are treated like
bonds to duplicate atoms.
=>
Chapter 5
7
Assign Priorities
O 2 OH
C
Cl
3 C
4
H
H3C
1NH2
H
natural alanine
3
H
C
H C
1
O
CH2
*C 4
CH(CH )
CH2OH
expands to
3 2
2
Chapter 5
4
H3
*
2
Cl
1
C C
H C CH2
O
*C
CH(CH3)2
C
CH2OH
H
O
C
=>
8
Assign (R) or (S)
• Working in 3D, rotate molecule so that
lowest priority group is in back.
• Draw an arrow from highest to lowest
priority group.
• Clockwise = (R), Counterclockwise = (S)
Chapter 5
=>
9
Properties of Enantiomers
•
•
•
•
Same boiling point, melting point, density
Same refractive index
Different direction of rotation in polarimeter
Different interaction with other chiral
molecules
– Enzymes
– Taste buds, scent
=>
Chapter 5
10
Optical Activity
• Rotation of plane-polarized light
• Enantiomers rotate light in opposite directions,
but same number of degrees.
=>
Chapter 5
11
Polarimetry
•
•
•
•
•
Use monochromatic light, usually sodium D
Movable polarizing filter to measure angle
Clockwise = dextrorotatory = d or (+)
Counterclockwise = levorotatory = l or (-)
Not related to (R) and (S)
Chapter 5
=>
12
Specific Rotation
Observed rotation depends on the length
of the cell and concentration, as well as
the strength of optical activity,
temperature, and wavelength of light.
[] =  (observed)
cl
c is concentration in g/mL
l is length of path in decimeters.
=>
Chapter 5
13
Calculate []D
• A 1.00-g sample is dissolved in 20.0 mL
ethanol. 5.00 mL of this solution is
placed in a 20.0-cm polarimeter tube at
25C. The observed rotation is 1.25
counterclockwise.
=>
Chapter 5
14
Biological Discrimination
=>
Chapter 5
15
Racemic Mixtures
•
•
•
•
Equal quantities of d- and l- enantiomers.
Notation: (d,l) or ()
No optical activity.
The mixture may have different b.p. and m.p.
from the enantiomers!
=>
Chapter 5
16
Racemic Products
If optically inactive reagents combine to
form a chiral molecule, a racemic
mixture of enantiomers is formed.
=>
Chapter 5
17
Optical Purity
• Also called enantiomeric excess.
• Amount of pure enantiomer in excess of
the racemic mixture.
• If o.p. = 50%, then the observed rotation
will be only 50% of the rotation of the
pure enantiomer.
• Mixture composition would be 75-25.
=>
Chapter 5
18
Calculate % Composition
The specific rotation of (S)-2-iodobutane is
+15.90. Determine the % composition of a
mixture of (R)- and (S)-2-iodobutane if the
specific rotation of the mixture is -3.18.
=>
Chapter 5
19
Chirality of Conformers
• If equilibrium exists between two chiral
conformers, molecule is not chiral.
• Judge chirality by looking at the most
symmetrical conformer.
• Cyclohexane can be considered to be
planar, on average.
=>
Chapter 5
20
Mobile Conformers
H
H
H H
Br
H
Br
Br
H
Br
Nonsuperimposable mirror images,
but equal energy and interconvertible.
Br Br
Use planar
approximation.
=>
Chapter 5
21
Nonmobile Conformers
If the conformer is sterically hindered, it
may exist as enantiomers.
=>
Chapter 5
22
Allenes
• Chiral compounds with no chiral carbon
• Contains sp hybridized carbon with
adjacent double bonds: -C=C=C• End carbons must have different groups.
=>
Allene is achiral.
Chapter 5
23
Fischer Projections
• Flat drawing that represents a 3D molecule
• A chiral carbon is at the intersection of
horizontal and vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.
Chapter 5
24
Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon at top.
• Rotation of 180 in plane doesn’t
change molecule.
• Do not rotate 90!
• Do not turn over out of plane! =>
Chapter 5
25
Fischer Mirror Images
• Easy to draw, easy to find enantiomers,
easy to find internal mirror planes.
• Examples:
CH3
CH3
CH3
H
Cl
Cl
H
H
Cl
Cl
H
H
Cl
H
Cl
CH3
CH3
CH3
Chapter 5
=>
26
Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so
assignment rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise
1-2-3 is (R).
• Example:
(S)
CH3
(S)
H
Cl
Cl
H
CH3
Chapter 5
=>
27
Diastereomers
• Stereoisomers that are not mirror images.
• Geometric isomers (cis-trans)
• Molecules with 2 or more chiral carbons.
=>
Chapter 5
28
Alkenes
Cis-trans isomers are not mirror images,
so these are diastereomers.
H
H
H
C C
C C
H3C
CH3
CH3
cis-2-butene
H3C
H
trans-2-butene
Chapter 5
=>
29
Ring Compounds
• Cis-trans isomers possible.
• May also have enantiomers.
• Example: trans-1,3-dimethylcylohexane
CH3
CH3
H
H
H
=>
H
CH3
CH3
Chapter 5
30
Two or More Chiral Carbons
• Enantiomer? Diastereomer? Meso? Assign
(R) or (S) to each chiral carbon.
• Enantiomers have opposite configurations at
each corresponding chiral carbon.
• Diastereomers have some matching, some
opposite configurations.
• Meso compounds have internal mirror plane.
• Maximum number is 2n, where n = the
number of chiral carbons.
=>
Chapter 5
31
Examples
COOH
COOH
H
HO
HO
OH
H
H
H
OH
COOH
COOH
(2S,3S)-tartaric acid
(2R,3R)-tartaric acid
COOH
H
OH
H
OH
COOH
(2R,3S)-tartaric acid
Chapter 5
=>
32
Fischer-Rosanoff Convention
• Before 1951, only relative configurations
could be known.
• Sugars and amino acids with same relative
configuration as (+)-glyceraldehyde were
assigned D and same as (-)-glyceraldehyde
were assigned L.
• With X-ray crystallography, now know
absolute configurations: D is (R) and L is (S).
• No relationship to dextro- or levorotatory.
=>
Chapter 5
33
D and L Assignments
CHO
H
*
CHO
OH
H
CH2OH
D-(+)-glyceraldehyde
HO
H
COOH
H2N
*
H
=>
CH2CH2COOH
L-(+)-glutamic
acid
Chapter 5
OH
H
OH
H *
OH
CH2OH
D-(+)-glucose
34
Properties of Diastereomers
• Diastereomers have different physical
properties: m.p., b.p.
• They can be separated easily.
• Enantiomers differ only in reaction with
other chiral molecules and the direction
in which polarized light is rotated.
• Enantiomers are difficult to separate.
=>
Chapter 5
35
Resolution of Enantiomers
React a racemic mixture with a chiral compound to
form diastereomers, which can be separated.
Chapter 5
=>
36
Chromatographic
Resolution of Enantiomers
=>
Chapter 5
37
End of Chapter 5
Chapter 5
38