CHEM 494
Special Topics in Chemistry
University of
Illinois at Chicago
Lecture 10
Stereochemistry
Duncan Wardrop
November 26, 2012
UIC
Historical Importance of Stereochemisty
Once a molecule is asymmetric, its extension proceeds also in an
asymmetrical sense. This concept completely eliminates the
difference between natural and artificial synthesis. The advance of
science has removed the last chemical hiding place for the once so
highly esteemed vis vitalis.
Emil Fischer, 1894
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 2
Lecture 10: November 26
Self Test Question
Which pair of molecules below are not
stereoisomers?
O
geometrical
H
stereoisomers A
conformational
stereoisomers
Stereoisomers:
1.same connectivity
2.different arrangement
of atoms in space
identical
molecules
UIC
H
CH3
BrCH
Br
O
3
O
C
H
enantiomeric
stereoisomers
University of
Illinois at Chicago
B
O
D
CHEM 494, Fall 2012
H
F
H
Br
F
Cl
Cl
H
Br
Slide 3
Lecture 10: November 26
Self Test Question
Which structure cannot be moved in space (translation) or
undergo rotation around single bonds to obtain a mirror image of
the molecule (1) below?
CH3
CH3
HO
Cl
CH3
OH
Cl
mirror image
1
2
CH3
OH
Cl
UIC
CH3
Cl
180 º
60º
HO
H 3C
A
B
CH3
identical to 1
CH3
OH
Cl
University of
Illinois at Chicago
Cl
HO
90 º
OH
Cl
CHEM 494, Fall 2012
Cl
OH
OH
60º
Cl
CH3
C
D
Slide 4
Lecture 10: November 26
Chirality
CH3
CH3
CH3
180 º
HO
Cl
OH
Cl
mirror image
1
2
Cl
HO
2
A molecule is chiral if its two mirror image forms are
not superimposable on one another
Superimposable molecules can be laid on top of
one another so that all equivalent atoms (points) line
up
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 5
Lecture 10: November 26
Chiral Objects
chiral: non-superimposable mirror images
snail
mirror
image
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 6
Lecture 10: November 26
Chiral Objects
chiral: non-superimposible mirror images
milkyway
University of
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mirror image
CHEM 494, Spring 2010
Slide 7
Lecture 10: November 26
Chirality
chiral: non-superimposible mirror images
fingerprint
University of
Illinois at Chicago
UIC
mirror image
CHEM 494, Spring 2010
Slide 8
Lecture 10: November 26
Chirality
chiral: non-superimposible mirror images
DNA double helix
University of
Illinois at Chicago
UIC
mirror image
CHEM 494, Spring 2010
Slide 9
Lecture 10: November 26
Chirality
chiral: non-superimposable mirror images
cheir (Greek) = hand
chirality is synonymous with “handedness”
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 10
Lecture 10: November 26
Molecules can Also Be Chiral
chiral: non-superimposible mirror images
Cl
Br
H
H
F
University of
Illinois at Chicago
UIC
Cl
Br
F
CHEM 494, Spring 2010
Slide 11
Lecture 10: November 26
Superimposibility
to check for superimposibility, rotate mirror image
180º along a plane perpendicular to the mirror plane
180º
Cl
Br
H
H
F
University of
Illinois at Chicago
UIC
Cl
Br
F
CHEM 494, Spring 2010
Slide 12
Lecture 10: November 26
Non-superimposible
if chiral:
the images
are not identical,
theyimages
are non
non-superimposible
mirror
superimposible; not all points (atoms) line up
Cl
Br
University of
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UIC
Br
Cl
H
F
H
F
CHEM 494, Spring 2010
Slide 13
Lecture 10: November 26
Not Everything is Chiral!
achiral: not chiral; mirror images are superimposible
basketball
University of
Illinois at Chicago
UIC
mirror image
CHEM 494, Spring 2010
Slide 14
Lecture 10: November 26
Not Everything is Chiral!
achiral: not chiral; mirror images are superimposible
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 15
Lecture 10: November 26
Not Everything is Chiral!
achiral: not chiral; mirror images are superimposible
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 16
Lecture 10: November 26
Symmetry Tests for Achiral Molecules
Any molecule with a plane of symmetry
or a center of symmetry is achiral (not
chiral)
A plane of symmetry bisects a molecule
into two mirror image halves
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 17
Lecture 10: November 26
Symmetry Tests for Achiral Molecules
Any molecule with a plane of symmetry
or a center of symmetry is achiral (not
chiral)
plane of symmetry
H3C
CH3
A plane of symmetry bisects a molecule
into two mirror image halves
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 18
Lecture 10: November 26
Symmetry Tests for Achiral Molecules
Any molecule with a plane of symmetry
or a center of symmetry is achiral (not
chiral)
Br
•
plane of symmetry
•
Cl
A plane of symmetry bisects a molecule
into two mirror image halves
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 19
Lecture 10: November 26
Symmetry Tests for Achiral Molecules
Any molecule with a plane of symmetry
or a center of symmetry is achiral (not
chiral)
plane of symmetry
Br C
H
Cl
C
H
A plane of symmetry bisects a molecule
into two mirror image halves
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 20
Lecture 10: November 26
Symmetry Tests for Achiral Molecules
Any molecule with a plane of symmetry
or a center of symmetry is achiral (not
chiral)
center of symmetry: a line drawn from
center of molecule to an element extends
in opposite direction to an identical
element
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 21
Lecture 10: November 26
Symmetry Tests for Achiral Molecules
Any molecule with a plane of symmetry
or a center of symmetry is achiral (not
chiral)
center of symmetry: a line drawn from
center of molecule to an element extends
in opposite direction to an identical
element
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 22
Lecture 10: November 26
Self Test Question
Which molecule below is chiral?
Cl
A
CH3
H 3C
Cl
B
Br Cl
H 3C
CH3
C
HO H
D
University of
Illinois at Chicago
UIC
CHEM 494, Fall 2012
CH2
Cl
CH3
Slide 23
Lecture 10: November 26
Chirality Center
Chirality center: an atom bonded to
ligands in a spatial arrangement
which is not superimposable on its
mirror image
Asymmetric carbon: a carbon atom
bonded to four different atoms or
groups (a type of chirality center)
W
Y C X
Z
University of
Illinois at Chicago
UIC
other terminology
commonly used:
•stereocenter
•stereogenic center
CHEM 494, Spring 2010
avoid these terms;
both have different
meanings from chirality
center
Slide 24
Lecture 10: November 26
Chirality Center
A molecule with a single chirality center is chiral
Br
F C H
Cl
University of
Illinois at Chicago
UIC
bromochlorofluoromethane is chiral
CHEM 494, Spring 2010
Slide 25
Lecture 10: November 26
Chirality Center
A molecule with a single chirality center is chiral
OH
H3C C CH2CH3
H
University of
Illinois at Chicago
UIC
• 2-butanol is chiral
• although two carbon atoms are
bonded to the chirality center,
they are part of different groups
CHEM 494, Spring 2010
Slide 26
Lecture 10: November 26
Chirality Center
A molecule with a single chirality center is chiral
CH3
H2C C
O H
University of
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UIC
• 1,2-epoxypropane: a chirality
center can be part of a ring
• attached to the chirality center are:
-H
-CH3
-CH2O
-OCH2
CHEM 494, Spring 2010
Slide 27
Lecture 10: November 26
Chirality Center
A molecule with a single chirality center is chiral
H
D C CH3
T
University of
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UIC
chiral as a result of
isotopic substitution
CHEM 494, Spring 2010
Slide 28
Lecture 10: November 26
1 Chirality Center = Chiral
A molecule with a single chirality center must be
chiral.
But a molecule with two or more chirality centers may
be chiral or it may not be chiral (Sections 7.10-7.13)
Br
F C H
Cl
CH3
H2C C
O H
CH3
OH
Cl
University of
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UIC
OH
H3C C CH2CH3
H
H
D C CH3
T
CHEM 494, Spring 2010
Slide 29
Lecture 10: November 26
Self Test Question
How many chirality centers in a molecule of
codeine?
CH3
N
A. 7
B. 6
C. 5
H3CO
University of
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UIC
O
H
OH
CHEM 494, Fall 2012
D. 4
E. 3
Slide 30
Lecture 10: November 26
CHEM 494
Special Topics in Chemistry
University of
Illinois at Chicago
UIC
Cahn–Ingold–Prelog (CIP)
Priority Rules
R-S Notation for
Chirality Centers
CIP R/S Notation
Step One: Locate chirality
center
chirality center
CH3
C
HO
Cl
University of
Illinois at Chicago
UIC
H
CHEM 494, Spring 2010
Slide 32
Lecture 10: November 26
CIP R/S Notation
Step Two: Orient molecule so that lowest
ranked (CIP priority) atom or group points
away from you
chirality center
HO
Cl
University of
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CH3
CH3 H
C
C
H
HO
CHEM 494, Spring 2010
Cl
Slide 33
Lecture 10: November 26
CIP R/S Notation
Step Three: Number 3 highest priority groups
in order of increasing priority (CIP sequence
rules)
chirality center
HO
Cl
University of
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3
CH3
CH3 H
C
C
H
2
HO
CHEM 494, Spring 2010
1
Cl
Slide 34
Lecture 10: November 26
CIP R/S Notation
Step Four: Determine rotation direction of
groups in decreasing priority
chirality center
HO
CH3
CH3 H
C
C
Cl
(R)-1chloroethanol
University of
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UIC
3
H
2
HO
1
Cl
clockwise (rectus) = R
counterclockwise (sinister) = S
CHEM 494, Spring 2010
Slide 35
Lecture 10: November 26
Self Test Question
Which molecule has a chirality center with
an absolute configuration of R?
Cl
clockwise = R
A
H
Br
F
2
3
HO H
B
1
H
OH
C
O
HO
CH3
D
H CH3
University of
Illinois at Chicago
UIC
CHEM 494, Fall 2012
Slide 36
Lecture 10: November 26
Enantiomers
molecules which are non-superimposible mirror
images are called enantiomers;
enantiomer describes a relationship between two
molecules (enantiomer: opposite handedness)
OH
enantiomers
(S)-2-butanol
OH
180 º
OH
(R)-2-butanol
enantiomers have opposite
configurations (R/S) at every chirality
center
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 37
Lecture 10: November 26
Enantiomers
molecules which are non-superimposible mirror
images are called enantiomers;
enantiomer describes a relationship between two
molecules (enantiomer: opposite handedness)
CH3
HO
Cl
enantiomers
CH3
OH
Cl
(S)-2-chloro-2-butanol
180 º
CH3
Cl
HO
(R)-2-chloro-2-butanol
enantiomers have opposite
configurations (R/S) at every chirality
center
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 38
Lecture 10: November 26
Isomers
isomers
Do the molecules have
the same connectivity?
constitutional
(structural)
no
yes
stereoisomers
Can the molecules be
interconverted by rotation
around single bonds?
yes
conformational
University of
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CHEM 494, Spring 2010
no
configurational
Slide 39
Lecture 10: November 26
Stereoisomers
configurational
stereoisomers
Is the isomerism at a
doulbe bond?
yes
no
geometrical
optical
Are the compounds nonsuperimposible mirror
images?
no
yes
enantiomers
University of
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UIC
CHEM 494, Spring 2010
diastereomers
Slide 40
Lecture 10: November 26
Self Test Question
Which pair of molecules are
enantiomers?
Cl Br
A H H
Remember: if a molecule has a
plane or center of symmetry, it is
not chiral and therefore has no
enantiomers.
University of
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UIC
B
HO H
C
HO H
Br
Cl
H
H
H OH
H H
OH
D
CHEM 494, Fall 2012
OH
CH3
CH3
OH
Slide 41
Lecture 10: November 26
Self Test Question
Which molecule is (R)-1-hexen-3-ol?
A
OH
B
OH
clockwise = R
1
HO H
3
C
2
D
H OH
E
HO H
University of
Illinois at Chicago
UIC
CHEM 494, Fall 2012
Slide 42
Lecture 10: November 26
Self Test Question
The three asymmetric carbon atoms in penicillin G
are labeled a-c. List the R/S configuration of each
in order of a,b,c.
A. R,R,S
a b
H
N
B. S,S,R
O
N
OH
c
UIC
D. S,R,S
H
O
University of
Illinois at Chicago
C. R,S,R
S
O
CHEM 494, Fall 2012
E. S,R,R
Slide 43
Lecture 10: November 26
Self Test Question
The three asymmetric carbon atoms in
penicillin G are labeled a-c. List the R/S
configuration of each in order of a,b,c.
A. R,R,S
a
B. S,S,R
N(CCH) H
S(SC)
N
O
N
H
O
C(OON)
University of
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C. R,S,R
S
OH
O
CHEM 494, Fall 2012
D. S,R,S
E. S,R,R
Slide 44
Lecture 10: November 26
Self Test Question
The three asymmetric carbon atoms in
penicillin G are labeled a-c. List the R/S
configuration of each in order of a,b,c.
A. R,R,S
b
H
N
O
B. S,S,R
C. R,S,R
S
N
D. S,R,S
H
O
OH
O
University of
Illinois at Chicago
UIC
CHEM 494, Fall 2012
E. S,R,R
Slide 45
Lecture 10: November 26
Self Test Question
The three asymmetric carbon atoms in
penicillin G are labeled a-c. List the R/S
configuration of each in order of a,b,c.
A. R,R,S
B. S,S,R
H
N
C(SCC)
S
O
N
OH
c
University of
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UIC
D. S,R,S
H
O
O
C. R,S,R
C(OOO)
CHEM 494, Fall 2012
E. S,R,R
Slide 46
Lecture 10: November 26
Self Test Question
The three asymmetric carbon atoms in
penicillin G are labeled a-c. List the R/S
configuration of each in order of a,b,c.
A. R,R,S
B. S,S,R
a b
H
N
O
N
OH
c
UIC
D. S,R,S
H
O
University of
Illinois at Chicago
C. R,S,R
S
O
CHEM 494, Fall 2012
E. S,R,R
Slide 47
Lecture 10: November 26
Self Test Question
List the R/S configuration of each
asymmetric carbon in the enantiomer of
penicillin G in the order a,b,c.
Remember: enantiomers have
opposite configurations at every
chirality center.
H
N
a
(R)
(R)
b S
O
O
N
(S)c
O
penicillin G
University of
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UIC
b
S
H
H
OH
c
HO
O
H
N
a
O
N
O
enantiomer of
penicillin G
CHEM 494, Fall 2012
A. R,R,S
B. S,S,R
C. R,S,R
D. S,R,S
E. S,R,R
Slide 48
Lecture 10: November 26
Stereoisomers with >1 Chirality Center
HO H
5
4
3
2
1
Cl H
(2S,3R)-3-chloro-2-hexanol or (2S,3R)-3-chlorohexan2-ol
Steps:
1. Number longest chain so that highest priority group has lowest locant.
2. List locants of asymmetric carbons in increasing order within parentheses at the beginning of
name.
3. List stereodescriptor (R/S) after each asymmetric locant.
Conventions/Rules:
• R & S are italicized when typed
• a comma separates each steredescriptor (no spaces)
• stereodescriptors are not considered when alphabetizing subgroups
• asymmetric locants are not written if their exclusion is unambiguous
(
chiral
locant
University of
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R/S
UIC
,
chiral
locant
R/S
)-
parent
CHEM 494, Fall 2012
class suffix
Slide 49
Lecture 10: November 26
Drawing Fisher Projections
HO H
H
Br
H Br
bond-line
H
Newman Projection
H
Br
OH
H
OH
Sawhorse Projection
CH3
HO
H
Br
H
Fisher Projection
Step One: Draw (imagine) totally eclipsed
conformation
HO H
Br
H
H
University of
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H
CHEM 494, Spring 2010
Slide 50
Lecture 10: November 26
Drawing Fisher Projections
HO H
H
Br
H Br
bond-line
H
Br
OH
H
H
Newman Projection
OH
Sawhorse Projection
CH3
HO
H
Br
H
Fisher Projection
Step Two: Imagine that the carbon skeleton atoms
form a “C” and you are looking at the back of the C.
HO H
Br
H
H
University of
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H
HO
H
Br
H
H
H
CHEM 494, Spring 2010
Slide 51
Lecture 10: November 26
Drawing Fisher Projections
HO H
H
Br
H Br
bond-line
H
Br
OH
H
H
Newman Projection
OH
Sawhorse Projection
CH3
HO
H
Br
H
Fisher Projection
Step Three: Flatten out the “C” so vertical bonds
point away from you and horizontal toward you.
HO H
Br
H
H
University of
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UIC
H
HO
H
Br
H
H
H
CHEM 494, Spring 2010
CH3
HO
H
Br
H
H
H
CH3
Slide 52
Lecture 10: November 26
Self Test Question
Which Fisher project is (2R,3R)-2,3-pentandiol?
HO H
HO H
HO
H
University of
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UIC
B
CH3
HO
H
H
OH
H
H
CH3
H
H
C
CH3
HO
H
HO
H
H
H
CH3
D
CH3
H
OH
HO
H
H
H
CH3
H
OH
HO H
A
CH3
H
OH
H
OH
H
H
CH3
H
OH
HH
CHEM 494, Fall 2012
Slide 53
Lecture 10: November 26
Properties of Enantiomers
CH3
O
H
(R)-(-)-carvone
boiling point = 231 ºC
density = 0.96
1H-NMR δs = same as (S)
13C-NMR δs = same as (S)
IR spectrum ῡs = same as
(S)
optical rotation = –61º
smell = earthy
boiling point = 231 ºC
density = 0.96
O
1H-NMR δs = same as (R)
13C-NMR δs = same as (R)
IR spectrum ῡs = same as
H
(R)
rotation = +61º
(S)-(+)-carvoneoptical
smell = spearmint
CH3
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 54
Lecture 10: November 26
Properties of Enantiomers
(S)-(+)-Carvone
(S)-carvone is the
enantiomer of (R)carvone
Enantiomers have the
same physical
properities including IR
vibrational frequencies,
mp, bp, Rf, etc.
(R)-(-)-Carvone
IR spectra for both
enantiomers of carvone-and for any two
enantiomeric
compounds--are
identical.
University of
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CHEM 494, Spring 2010
Slide 55
Lecture 10: November 26
Optical Rotation
(–) = counterclockwise = levorotary
(+) = clockwise = dextrorotary
enantiomers rotate plane polarized light an
equal magnitude, but in opposite directions
University of
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CHEM 494, Spring 2010
Slide 56
Lecture 10: November 26
Optical Rotation
•
degree of optical rotation depends on concentration of a
solution containing the chiral compound
•
[α]: specific optical rotation; determined in specified
concenetration and path length units for universal
comparison
[α] =
25
D
(100)(α)
(c)(l)
α = degree of rotation determined by polarimeter
c = concentration (g/dL); 10 dL = 1 L
l = path length (cm)
University of
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CHEM 494, Spring 2010
Slide 57
Lecture 10: November 26
Optical Rotation
racemic mixture = contains equal quantities of both
enantiomers (1:1, 50/50, etc); [α] = 0º
•
enantiomeric excess (ee) = |% A enantiomer - % B
enantiomer|
racemic mixture
•
University of
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% A enantiomer % B enantiomer
enantiomeric
excess (ee)
100
0
100
75
25
50
50
50
0
25
75
50
0
100
100
UIC
CHEM 494, Spring 2010
Slide 58
Lecture 10: November 26
R/S versus (+)/(-)
• Enantiomers have equal magnitudes, but
opposite signs of specific rotation
• Caution: the sign of rotation (+/-) cannot be
determined from R/S configuration!
CH3
CH3
O
O
O
O
H
O
N
O
O
(S)-(+)-carvone
[] = +61º
University of
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H N
O
H
(R)-(–)-carvone
[] = –61º
(S)-(–)-thalidomide
[] = –64º
CHEM 494, Spring 2010
H
N
N H
H
O
O
(R)-(+)-thalidomide
[] = +64º
Slide 59
Lecture 10: November 26
Diastereomers:Chiral Molecules with >1
Chirality Center
University of
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diastereomers:
•stereoisomers that
are not mirror
images
•stereoisomers with
≥ 2 chirality centers
that are not all
opposite
•diastereomers may
have different
physical properties!
CHEM 494, Spring 2010
Slide 60
Lecture 10: November 26
Meso Forms
meso forms = achiral molecules with chirality centers
meso forms are optically inactive (0º optical rotation)
H OH
S R
HO H
HO H
H OH
HO H
R S
R R
H OH
S S
H OH
HO H
Two tests for meso:
H OH
OH
H
meso
University of
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HO H
H
OH
meso
1.plane or center of symmetry
2.two chirality centers with same
groups, but opposite
configurations
CHEM 494, Spring 2010
Slide 61
Lecture 10: November 26
Determining the Number of Stereoisomers
2n = maximum number of stereoisomers
n = chirality centers
OH OH O
HO
H
OH OH
2n = 24 = 16 stereoisomers
University of
Illinois at Chicago
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CHEM 494, Spring 2010
Slide 62
Lecture 10: November 26
Determining the Number of Stereoisomers
2n = maximum number of stereoisomers
n = chirality centers
alkenes that have
geometrical isomers
are also a type of
chirality center!
HO H
2n = 22 = 4 stereoisomers
University of
Illinois at Chicago
UIC
CHEM 494, Spring 2010
Slide 63
Lecture 10: November 26
Determining the Number of Stereoisomers
2n = maximum number of stereoisomers
n = chirality centers
OH
OH
O
OH
2n = 23 = 8 stereoisomers
University of
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UIC
CHEM 494, Spring 2010
Slide 64
Lecture 10: November 26
Self-Test Question
Thyrotropin releasing hormone (TRH) stimulates the
anterior pituitary to release thyroid stimulating hormone
(TSH); the thyroid gland regulates metabolism. How
many stereoisomers are possible in TRH?
HN
N
O
N
O
O
N
H
H
N
O
NH2
TRH
University of
Illinois at Chicago
UIC
CHEM 494, Fall 2012
A.
B.
C.
D.
E.
2
4
8
16
32
Slide 65
Lecture 10: November 26