Chapter 5
Stereochemistry
Jo Blackburn
Richland College,Dallas,TX
Dallas County Community College District
2003,Prentice Hall
Organic Chemistry,5th Edition
L,G,Wade,Jr.
Chapter 5 2
Chirality
,Handedness”,right glove doesn’t fit the
left hand.
Mirror-image object is different from the
original object,=>
Chapter 5 3
Stereoisomers
Geometric isomers,cis-trans isomers.
Enantiomers,nonsuperimposable mirror
images,different molecules,
=>
cis-1,2-dichlorocyclopentane trans -1,2-dichlorocyclopentane
H
C l
H
C l
H
C l
H
C l
H
C l
C l
H
H
C l
C l
H
Chapter 5 4
Chiral Carbons
Tetrahedral carbons with 4 different
attached groups are chiral.
Its mirror image will be a different
compound (enantiomer),=>
Chapter 5 5
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 6
(R),(S) Nomenclature
Different molecules (enantiomers) must
have different names.
Usually only one enantiomer will be
biologically active.
Configuration around the
chiral carbon is specified
with (R) and (S),
C
C
O O H
H 3 C
N H 2
H
n a t u r a l a l a n i n e=>
Chapter 5 7
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 8
Assign Priorities
C
C
O O H
H 3 C
N H 2
H
n a t u r a l a l a n i n e
1
2
3 4
C l
HC l
H
*
1
2
3
4
1 2
3
4
=>
C
C
O
H
C
H C H
2
C H 2 O H
C H ( C H 3 ) 2
*
C
C
C
C H 2 O H
C H ( C H 3 ) 2
H
O
O
C
C
H C H 2
C
*expands to
Chapter 5 9
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 10
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 11
Optical Activity
Rotation of plane-polarized light
Enantiomers rotate light in opposite directions,
but same number of degrees,
=>
Chapter 5 12
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 13
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 14
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 15
Biological Discrimination
=>
Chapter 5 16
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 17
Racemic Products
If optically inactive reagents combine to
form a chiral molecule,a racemic
mixture of enantiomers is formed.
=>
Chapter 5 18
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 19
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 20
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 21
Mobile Conformers
H
B r
H
B r
H
B r
H
B r
Nonsuperimposable mirror images,
but equal energy and interconvertible.
BrBr
H H
Use planar
approximation.
=>
Chapter 5 22
Nonmobile Conformers
If the conformer is sterically hindered,it
may exist as enantiomers.
=>
Chapter 5 23
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 24
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 25
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 26
Fischer Mirror Images
Easy to draw,easy to find enantiomers,
easy to find internal mirror planes.
Examples:
C H 3
H C l
C l H
C H 3
C H 3
C l H
H C l
C H 3
C H 3
H C l
H C l
C H 3
=>
Chapter 5 27
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:
C H 3
H C l
C l H
C H 3
(S)
(S) =>
Chapter 5 28
Diastereomers
Stereoisomers that are not mirror images.
Geometric isomers (cis-trans)
Molecules with 2 or more chiral carbons,
=>
Chapter 5 29
Alkenes
Cis-trans isomers are not mirror images,
so these are diastereomers.
C C
H H
C H 3H 3 C
c is - 2 - b u t e n e tr a n s - 2 - b u t e n e
C C
H
H 3 C
C H 3
H=>
Chapter 5 30
Ring Compounds
Cis-trans isomers possible.
May also have enantiomers.
Example,trans-1,3-dimethylcylohexane
C H 3
H
H
C H 3
C H 3
H
H
C H 3
=>
Chapter 5 31
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 32
ExamplesC O O H
H O H
H O H
C O O H
(2 R,3 R ) - t a r t a r i c a c i d
C O O H
C O O H
H O H
H O H
(2 S,3 S ) - t a r t a r i c a c i d
=> (2 R,3 S ) - t a r t a r i c a c i d
C O O H
C O O H
H O H
H O H
Chapter 5 33
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 34
D and L Assignments
C H O
H O H
C H 2 O H
D - ( + ) - g l y c e r a l de h y d e
*
C H O
H O H
H O H
H O H
H O H
C H
2
O H
D - ( +) - g l u c o s e
*
C O O H
H 2 N H
C H 2 C H 2 C O O H
L - ( +) - g l u t a m i c a c i d
*
=>
Chapter 5 35
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 36
Resolution of Enantiomers
React a racemic mixture with a chiral compound to
form diastereomers,which can be separated.
=>
Chapter 5 37
Chromatographic
Resolution of Enantiomers
=>
Chapter 5 38
End of Chapter 5
Stereochemistry
Jo Blackburn
Richland College,Dallas,TX
Dallas County Community College District
2003,Prentice Hall
Organic Chemistry,5th Edition
L,G,Wade,Jr.
Chapter 5 2
Chirality
,Handedness”,right glove doesn’t fit the
left hand.
Mirror-image object is different from the
original object,=>
Chapter 5 3
Stereoisomers
Geometric isomers,cis-trans isomers.
Enantiomers,nonsuperimposable mirror
images,different molecules,
=>
cis-1,2-dichlorocyclopentane trans -1,2-dichlorocyclopentane
H
C l
H
C l
H
C l
H
C l
H
C l
C l
H
H
C l
C l
H
Chapter 5 4
Chiral Carbons
Tetrahedral carbons with 4 different
attached groups are chiral.
Its mirror image will be a different
compound (enantiomer),=>
Chapter 5 5
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 6
(R),(S) Nomenclature
Different molecules (enantiomers) must
have different names.
Usually only one enantiomer will be
biologically active.
Configuration around the
chiral carbon is specified
with (R) and (S),
C
C
O O H
H 3 C
N H 2
H
n a t u r a l a l a n i n e=>
Chapter 5 7
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 8
Assign Priorities
C
C
O O H
H 3 C
N H 2
H
n a t u r a l a l a n i n e
1
2
3 4
C l
HC l
H
*
1
2
3
4
1 2
3
4
=>
C
C
O
H
C
H C H
2
C H 2 O H
C H ( C H 3 ) 2
*
C
C
C
C H 2 O H
C H ( C H 3 ) 2
H
O
O
C
C
H C H 2
C
*expands to
Chapter 5 9
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 10
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 11
Optical Activity
Rotation of plane-polarized light
Enantiomers rotate light in opposite directions,
but same number of degrees,
=>
Chapter 5 12
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 13
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 14
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 15
Biological Discrimination
=>
Chapter 5 16
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 17
Racemic Products
If optically inactive reagents combine to
form a chiral molecule,a racemic
mixture of enantiomers is formed.
=>
Chapter 5 18
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 19
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 20
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 21
Mobile Conformers
H
B r
H
B r
H
B r
H
B r
Nonsuperimposable mirror images,
but equal energy and interconvertible.
BrBr
H H
Use planar
approximation.
=>
Chapter 5 22
Nonmobile Conformers
If the conformer is sterically hindered,it
may exist as enantiomers.
=>
Chapter 5 23
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 24
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 25
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 26
Fischer Mirror Images
Easy to draw,easy to find enantiomers,
easy to find internal mirror planes.
Examples:
C H 3
H C l
C l H
C H 3
C H 3
C l H
H C l
C H 3
C H 3
H C l
H C l
C H 3
=>
Chapter 5 27
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:
C H 3
H C l
C l H
C H 3
(S)
(S) =>
Chapter 5 28
Diastereomers
Stereoisomers that are not mirror images.
Geometric isomers (cis-trans)
Molecules with 2 or more chiral carbons,
=>
Chapter 5 29
Alkenes
Cis-trans isomers are not mirror images,
so these are diastereomers.
C C
H H
C H 3H 3 C
c is - 2 - b u t e n e tr a n s - 2 - b u t e n e
C C
H
H 3 C
C H 3
H=>
Chapter 5 30
Ring Compounds
Cis-trans isomers possible.
May also have enantiomers.
Example,trans-1,3-dimethylcylohexane
C H 3
H
H
C H 3
C H 3
H
H
C H 3
=>
Chapter 5 31
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 32
ExamplesC O O H
H O H
H O H
C O O H
(2 R,3 R ) - t a r t a r i c a c i d
C O O H
C O O H
H O H
H O H
(2 S,3 S ) - t a r t a r i c a c i d
=> (2 R,3 S ) - t a r t a r i c a c i d
C O O H
C O O H
H O H
H O H
Chapter 5 33
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 34
D and L Assignments
C H O
H O H
C H 2 O H
D - ( + ) - g l y c e r a l de h y d e
*
C H O
H O H
H O H
H O H
H O H
C H
2
O H
D - ( +) - g l u c o s e
*
C O O H
H 2 N H
C H 2 C H 2 C O O H
L - ( +) - g l u t a m i c a c i d
*
=>
Chapter 5 35
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 36
Resolution of Enantiomers
React a racemic mixture with a chiral compound to
form diastereomers,which can be separated.
=>
Chapter 5 37
Chromatographic
Resolution of Enantiomers
=>
Chapter 5 38
End of Chapter 5
