Chapter 12
Stereochemistry
Chapter 6
1
Isomer Organization
Isomers
Stereoisomers
Enantiomers
Geometric
Cis/trans
Constitutional isomers
Diastereomers
Conformational
Isomers
Chapter 6
Meso
compounds
Epimers
2
Stereoisomers
• Same bonding sequence.
• Different arrangement in space.
• Example: HOOC-CH=CH-COOH
has two geometric (cis-trans) isomers
O
H
C OH
O
HO C
C C
HO C
O
C OH
C C
H
O
fumaric acid, mp 287 o C
essential metabolite
H
H
=>
maleic acid, mp 138 o C
toxic irritant
Chapter 6
3
Chirality
• “Handedness”: right glove doesn’t fit the left
hand.
• Mirror-image object is different from the
original object
Chapter 6
4
Examples of Handed Objects
•
•
•
•
•
Your hands, from the previous slide
Gloves
Scissors
Screws
Golf clubs
Chapter 6
5
How about molecules?
• Chemical substances can be handed
• Handed substances are said to be chiral
• Molecules, that are chiral are
nonsuperimposable on their mirror image
Chapter 6
6
Chirality in Molecules
• cis isomers are achiral (not chiral).
Chapter 6
7
Chirality in Molecules
• The cis isomer is achiral.
• The trans isomer is chiral.
Chapter 6
8
Chirality in Molecules
• The cis isomer is achiral.
• The trans isomer is chiral.
• Enantiomers: nonsuperimposable mirror
images, different molecules.
Chapter 6
9
Chirality in Molecules
• The cis isomer is achiral.
• The trans isomer is chiral.
• Enantiomers: nonsuperimposable mirror
images, different molecules.
• One enantiomeric form of limonene smells
like oranges, while its mirror image smells like
lemons.
Chapter 6
10
Chirality in Molecules
• The cis isomer is achiral.
• The trans isomer is chiral.
• Enantiomers: nonsuperimposable mirror images,
different molecules.
• One enantiomeric form of limonene smells like
oranges, while its mirror image smells like lemons.
• The one enantiomer of carvone is the essence of
caraway, and the other, the essence of spearmint.
• Most molecules in the plant and animal world are
chiral and usually only one form of then enantiomer is
found.
Chapter 6
11
Chirality in Molecules
• The cis isomer is achiral.
• The trans isomer is chiral.
• Enantiomers: nonsuperimposable mirror images,
different molecules.
• One enantiomeric form of limonene smells like
oranges, while its mirror image smells like lemons.
• The one enantiomer of carvone is the essence of
caraway, and the other, the essence of spearmint.
• Most molecules in the plant and animal world are
chiral and usually only one form of then enantiomer is
found.
• Nineteen of the twenty known amino acids are chiral,
and all of them are classified as left handed.
Chapter 6
12
Chirality in Molecules
• The cis isomer is achiral.
• The trans isomer is chiral.
• Enantiomers: nonsuperimposable mirror
images, different molecules.
Chapter 6
13
Stereocenters
• Any atom at which the exchange of two
groups yields a stereoisomer.
• Examples:
• Asymmetric carbons
• Double-bonded carbons in cis-trans isomers
=>
Chapter 6
14
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 6
15
(R), (S) Nomenclature
Called Absolute Configuration
• Called the Cahn-Ingold-Prelog convention
• 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).
Chapter 6
16
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 6
17
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 6
18
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 6
19
Plane-Polarized Light
• Polarizing filter –
calcite crystals or
plastic sheet.
• When two filters
are used, the
amount of light
transmitted
depends on the
angle of the axes.
Chapter 6
20
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 6
21
Biological Discrimination
Chapter 6
22
Racemic Mixtures
• Equal quantities of d- and l- enantiomers a
50/50 mixture.
• Notation: (d,l) or ()
• No optical activity.
• The mixture may have different b.p. and m.p.
from the enantiomers!
Chapter 6
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 6
24
Fischer Rules
• Carbon chain is on the vertical line.
• Horizontal bonds pointing up with respect to the
plane of the paper.
• Vertical bonds pointing down with respect to the
plane of the paper.
• 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 6
25
Fischer Structures
• 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
A meso compound
Chapter 6
26
Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so
assignment rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise 12-3 is (R).
• Example:
(S)
CH3
(S)
H
Cl
Cl
H
Mirror image, both
would be R
CH3
Chapter 6
27
Diastereomers
• Stereoisomers that are not mirror images.
• Molecules with 2 or more chiral carbons.
• Geometric isomers (cis-trans), since they are
not mirror images.
H
H
H
C C
C C
H3C
CH3
CH3
cis-2-butene
H3C
H
trans-2-butene
Chapter 6
28
Ring Compounds
• Cis-trans isomers possible.
• May also have enantiomers.
• Example: trans-1,2-dimethylcyclopentane
=>
Chapter 6
29
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 6
30
Examples
COOH
COOH
H
*
OH
HO
*
H
COOH
HO
*
H
H
*
OH
enantiomers
(2R,3R)-tartaric acid
COOH
(2S,3S)-tartaric acid
COOH
H
* OH
H
* OH
A meso compound, contains 2 or
more stereocenters and a plane
of symmetry
COOH
(2R,3S)-tartaric acid
Chapter 6
31
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, we now know absolute
configurations: D is (R) and L is (S).
• No relationship to dextro- or levorotatory, meaning
that some D enantiomers are (R) and some are (S).
• Anyone who can look at a structure and determine
which way it will rotate polarized light receives an
automatic Noble Prize! There is a lot we do not know!
Chapter 6
32
D and L Assignments
CHO
*
H
OH
CH2OH
Penultimate carbon is the
stereocenter farthest away
from the carbonyl group. If
the higher priority group is on
the left, then (L), if on the right
then (D) sugar.
D-(+)-glyceraldehyde
COOH
H2N
*
H
CH2CH2COOH
L-(+)-glutamic
CHO
H
*
OH
HO
*
H
H
*
OH
H
* OH
CH2OH
D-(+)-glucose
acid
Chapter 6
33
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 6
34
Resolution of Enantiomers
• Pasteur was the first to resolve an enatiomeric
mixture, using a magnifying glass and
tweezers.
• Animals can consume a racemate and
metabolize on of the tow enantiomers, while
the other is recovered in their waste products.
• Chemical means, described on the next slide
Chapter 6
35
Chemical Resolution of Racemate
• React a racemic mixture with a chiral
compound to form diastereomers, which can
Chapter 6
36
Stereochemistry Review
Chapter 6
37
Compare the physical properties of
enantiomers.
a. Different physical properties.
b.Same physical properties.
c. Cannot determine.
d.Same chemical properties.
Chapter 6
38
Answer
a. Different physical properties.
b.Same physical properties.
c. Cannot determine.
d.Same chemical properties.
Enantiomers have the same physical
properties, such as melting point or boiling
point.
Chapter 6
39
Identify as R, S, or achiral.
Br
Cl
C
CH3
H
a.
b.
c.
d.
R
S
Achiral
Cannot be determined.
Chapter 6
40
Answer
a.
b.
c.
d.
R
S
Achiral
Cannot be determined.
Br > Cl > CH3 > H
Chapter 6
41
Identify as R, S, or achiral.
I
H
C
CH2CH3
CH3
a.
b.
c.
d.
R
S
Achiral
Cannot be determined.
Chapter 6
42
Answer
a.
b.
c.
d.
R
S
Achiral
Cannot be determined.
I > CH3CH2 > CH3 > H
Chapter 6
43
Identify as R, S, or achiral.
CH3CH2
a.
b.
c.
d.
CH2CH2CH3
CH3
C
CH
CH3
CH3
R
S
Achiral
Cannot be determined.
Chapter 6
44
Answer
a.
b.
c.
d.
R
S
Achiral
Cannot be determined.
CH(CH3)2 > CH2CH2CH3 > CH2CH3 > CH3
Chapter 6
45
Identify as R, S, or achiral.
CH2CH3
H3C
C
HC
a.
b.
c.
d.
CH(CH3)2
CH2
R
S
Achiral
Cannot be determined.
Chapter 6
46
Answer
a.
b.
c.
d.
R
S
Achiral
Cannot be determined.
CH=CH2 > CH(CH3)2 > CH2CH3 > CH3
Chapter 6
47
Identify as R, S, or achiral.
CH3
H3C
CH
HC
a.
b.
c.
d.
C
R
HC
S
Achiral
Cannot be determined.
3
Chapter 6
C
CH3
CH3
48
Answer
a.
b.
c.
d.
R
S
Achiral
Cannot be determined.
C6H5 > HC≡C > C(CH3)3 > CH(CH3)2
Chapter 6
49
Identify the type isomer for (R) 2-pentanol.
a. Dextrorotatory isomer.
b.Levorotatory isomer.
c. Has to be experimentally determined.
d.Neither.
Chapter 6
50
Answer
a. Dextrorotatory isomer.
b.Levorotatory isomer.
c. Has to be experimentally determined.
d.Neither.
Dextrorotatory and levorotatory isomers
must be experimentally determined.
Chapter 6
51
Identify the type of alkene in
CH3CHCCH2.
a. Isolated diene.
b.Conjugated diene.
c. Allene.
d.Alkyne.
Chapter 6
52
Answer
a. Isolated diene.
b.Conjugated diene.
c. Allene.
d.Alkyne.
In an allene, two double bonds share a
carbon.
Chapter 6
53
Classify 2R,3S-2,3-dichloropentane and
2S,3S-2,3-dichloropentane.
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
Chapter 6
54
Answer
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
Diastereomers are stereoisomers that
are not mirror images.
Chapter 6
55
Classify 2S,3S-2,3-dichloropentane
and 2R,3R-2,3-dichloropentane.
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
Chapter 6
56
Answer
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
Enantiomers are mirror image isomers.
Chapter 6
57
Classify 2R,3S-2,3-dichlorobutane and
2S,3R-2,3-dichlorobutane.
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
Chapter 6
58
Answer
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
The compounds are identical.
Chapter 6
59
Classify 2R,3R-2,3-dichlorobutane and
2S,3S-2,3-dichlorobutane.
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
Chapter 6
60
Answer
a. Enantiomers
b.Diastereomers
c. Conformational isomers
d.Constitutional isomers
e.Identical
The compounds are enantiomers.
Chapter 6
61
Identify the number of stereoisomers
for 3-bromo-2,4,5-trichlorohexane.
a. 6 stereoisomers
b.8 stereoisomers
c. 12 stereoisomers
d.16 stereoisomers
e.24 stereoisomers
Chapter 6
62
Answer
a. 6 stereoisomers
b.8 stereoisomers
c. 12 stereoisomers
d.16 stereoisomers
e.24 stereoisomers
The number of stereoisomers is 24 or 16.
Chapter 6
63
Define meso compound.
a. A meso compound is an achiral molecule.
b.A meso compound has a plane of symmetry.
c. A meso compound has chiral carbons.
d.All of the above.
Chapter 6
64
Answer
a. A meso compound is an achiral molecule.
b. A meso compound has a plane of symmetry.
c. A meso compound has chiral carbons.
d. All of the above.
A meso compound has chiral carbons, is
achiral, and has a plane of symmetry.
Chapter 6
65
Identify a pair of diastereomers.
a. A and B
b.A and D
c. B and C
d.None
H
H
H
H
Br
C
Cl
Cl
C
Br
Br
C
Cl
Cl
C
Br
Br
C
Cl
Br
C
Cl
Cl
C
Br
Cl
C
Br
H
A
H
B
H
Chapter 6
C
H
D
66
Answer
a. A and B
b.A and D
c. B and C
d.None
Chapter 6
67
Identify a pair of enantiomers.
a. A and B
b.A and D
c. B and C
d.A and C
H
H
H
H
Br
C
Cl
Cl
C
Br
Br
C
Cl
Cl
C
Br
Br
C
Cl
Br
C
Cl
Cl
C
Br
Cl
C
Br
H
A
H
B
H
Chapter 6
C
H
D
68
Answer
a. A and B
b.A and D
c. B and C
d.A and C
Chapter 6
69
Identify a meso compound.
a. A
b.B
c. C
d.A and D
H
H
H
H
Br
C
Cl
Cl
C
Br
Br
C
Cl
Cl
C
Br
Br
C
Cl
Br
C
Cl
Cl
C
Br
Cl
C
Br
H
A
H
H
B
C
Chapter 6
H
D
70
Answer
a. A
b.B
c. C
d.A and D
Chapter 6
71
Compare the physical properties of
diastereomers.
a. Different physical properties.
b.Same physical properties.
c. Cannot determine.
d.Same chemical properties.
Chapter 6
72
Answer
a. Different physical properties.
b.Same physical properties.
c. Cannot determine.
d.Same chemical properties.
Diastereomers have different physical
properties, such as melting point or
boiling point.
Chapter 6
73
End of Chapter 12
Chapter 6
74