Download Ch 15 - Phillips Scientific Methods

Frederick A. Bettelheim
William H. Brown
Mary K. Campbell
Shawn O. Farrell
www.cengage.com/chemistry/bettelheim
Chapter 15
Chirality: The Handedness of
Molecules
William H. Brown • Beloit College
Isomers
Types of isomers
• In this chapter we study enantiomers and
diastereomers.
Is omers
same different
connectivity connectivity
Stereoisomers
Constitutional Isomers
without with
stereocenters stereocenters
Achiral
Cis-Trans Is omers
Chiral
Enantiomers
Diastereomers
15-2
Enantiomers
Enantiomers: Nonsuperposable mirror images.
• As an example of a molecule that exists as a pair of
enantiomers, consider 2-butanol.
OH
C H
H3 C
CH 2 CH 3
Origin al molecu le
HO
H C CH
3
CH3 CH2
Mirror image
15-3
Enantiomers
One way to see that the mirror image of 2-butanol is not
superposable on the original is to rotate the mirror image.
OH
C H
H3 C
CH2 CH3
Original molecule
180°
OH
H C CH
3
CH3 CH2
Mirror image
rotate by 180°
about the
C-OH b on d
OH
C CH CH
2
3
H3 C
H
The mirror image
rotated b y 180°
15-4
Enantiomers
• Now try to fit one molecule on top of the other so that
all groups and bonds match exactly.
OH
The mirror image
turn ed by 180°
C CH CH
2
3
H3 C
H
OH
The original molecule
C H
H3 C
CH2 CH3
• The original and mirror image are nonsuperposable.
• They are different molecules.
• Nonsuperposable mirror images are enantiomers.
15-5
Enantiomers
Objects that are nonsuperposable on their mirror images
are chiral (from the Greek: cheir, hand).
• They show handedness.
The most common cause of enantiomerism in organic
molecules is the presence of a carbon with four different
groups bonded to it.
• A carbon with four different groups bonded to it is
called a stereocenter.
15-6
Enantiomers
• If an object and its mirror image are superposable, they
are identical and there is no possibility of enantiomerism.
• We say that such an object is achiral (without chirality).
• As an example of an achiral molecule, consider 2propanol.
• notice that it has no stereocenter.
OH
C H
H3 C
CH3
Origin al molecu le
OH
H C CH
3
H3 C
Mirror image
15-7
Enantiomers
• To see the relationship between the original and its
mirror image, rotate the mirror image by 120°.
OH
C H
H3 C
CH3
Origin al molecu le
120° OH
H C CH
3
H3 C
Mirror image
rotate by 120°
about th e
C-OH bond
OH
C H
H3 C
CH3
The mirror image
rotated b y 120°
• When we do this rotation, we see that all atoms and
bonds of the mirror image fit exactly on the original.
• This means that the original and its mirror image are
the same molecule.
• They are just viewed from different perspectives.
15-8
Enantiomers
• To summarize;
• Objects that are nonsuperposable on their mirror
images are chiral (they show handedness).
• The most common cause of chirality among organic
molecules is the presence of a carbon with four
different groups bonded to it.
• We call a carbon with four different groups bonded to it
a stereocenter.
• Objects that are superposable on their mirror images
are achiral (without chirality).
• Nonsuperposable mirror images are called
enantiomers.
• Enantiomers always come in pairs.
15-9
The R,S System
Because enantiomers are different compounds, each
must have a different name.
• Here are the enantiomers of the over-the-counter drug
ibuprofen.
H
CH3
COOH
The inactive enan tiom er
H3 C H
HOOC
Th e activ e enantio mer
• The R,S system is a way to distinguish between
enantiomers without having to draw them and point to
one or the other.
HW:1- What is a racemic mixture?; 2- Why is ibuprophen sold as
a racemic mixture?; 3- What would be the effect if it weren’t?
*expect a test question on this!
15-10
The R,S System
The first step in assigning an R or S configuration to a
stereocenter is to arrange the groups on the stereocenter
in order of priority.
• Priority is based on atomic number.
• The higher the atomic number, the higher the priority.
• *Note: a double bond is treated as 2 single bonds to the
element. EX: C=O would be C-O-O when assigning
priority
15-11
R,S Priority of Some Groups
Atom or
Grou p
-I
-Br
-Cl
-SH
-OH
-N H 2
O
-COH
O
-CN H 2
O
-CH
-CH 2OH
-CH 2N H 2
-CH 2CH 3
-CH 2H
-H
Reason for Priority: First Point of D ifferen ce
(Atomic numbers)
iodine (53)
bromin e (35)
ch lorine (17)
su lfu r (16)
oxygen (8)
nitrogen (7)
carbon to oxygen, oxygen, th en oxygen (6 —> 8, 8, 8)
carbon to oxygen, oxygen, th en nitrogen (6 —> 8, 8, 7)
carbon to oxygen, oxygen, th en hydrogen (6 —> 8, 8, 1)
carbon to oxygen (6 —> 8)
carbon to nitrogen (6 —> 7)
carbon to carbon (6 —> 6)
carbon to hydrogen (6 —> 1)
hydrogen (1)
15-12
The R,S System
Example: Assign priorities to the groups in each set.
(a) -CH2 OH and -CH2 CH2 OH
(b) -CH2 CH2 OH and -CH2 NH2
O
(c) -CH2 OH and -CH2 CH2 COH
(d ) -CH2 NH2
O
and -CH2 COH
15-13
The R,S System
Example: Assign priorities to the groups in each set.
Solution:
(a) -CH2 OH and -CH2 CH2 OH
-CH2 OH
-CH2 CH2 OH
Higher priority Lower priority
O
(c) -CH2 OH and -CH2 CH2 COH
O
-CH2 OH
-CH2 CH2 COH
Higher priority Low er priority
(b) -CH2 CH2 OH and -CH2 NH2
-CH2 CH2 OH
-CH2 NH2
Lower priority Higher priority
O
(d) -CH2 NH2 and -CH2 COH
O
-CH2 NH2
-CH2 COH
Higher priority Low er priority
15-14
The R,S System
• To assign an R or S configuration:
1. Assign a priority from 1 (highest) to 4 (lowest) to each
group bonded to the stereocenter.
2. Orient the molecule in space so that the group of
lowest priority (4) is directed away from you. The three
groups of higher priority (1-3) then project toward you.
3. Read the three groups projecting toward you in order
from highest (1) to lowest (3) priority.
4. If reading the groups 1-2-3 is clockwise, the
configuration is R. If reading them is counterclockwise,
the configuration is S.
15-15
The R,S System
*Get a kit and construct the following 2 molecules
• Example: Assign an R or S configuration to each
stereocenter.
OH
(a)
C
H
CH2 CH3
2-Bu tanol
H3 C
H2 N H
(b)
C
H3 C
COOH
Alanin e
15-16
The R,S System
• Example: Assign an R or S configuration to each
stereocenter.
1
(a)
OH
4
C
3
H3 C
2
R
R
H
CH2 CH3
(R)-2-Butan ol
1
4
H2 N H
(b)
3
H3 C
C
R
R
2
COOH
(R)-Alanine
15-17
The R,S System
• Returning to our original three-dimensional drawings of
the enantiomers of ibuprofen.
4
3
3
H CH3
1
2
COOH
R
(R )-Ibuprofen
(the in acti ve en antiomer)
H3 C H4
1
2
HOOC
S
(S)-Ibuprofen
(the acti ve enenti omer)
15-18
Two or More Stereocenters
For a molecule with n stereocenters, the maximum
number of possible stereoisomers is 2n.
• We have already verified that, for a molecule with one
stereocenter, 21 = 2 stereoisomers (one pair of
enantiomers) are possible.
• For a molecule with two stereocenters, a maximum of
22 = 4 stereoisomers (two pair of enantiomers) are
possible.
• For a molecule with three stereocenters, a maximum of
23 = 8 stereoisomers (four pairs of enantiomers) are
possible, and so forth.
15-19
Two Stereocenters
2,3,4-Trihydroxybutanal
• Two stereocenters; 22 = 4 stereoisomers exist (two pairs of
enantiomers).
CHO
CHO
CHO
CHO
H
C
OH HO
C
H
H
C
OH HO
C
H
H
C
OH HO
C
H
HO
C
H
C
OH
CH2 OH
CH2 OH
(a)
(b)
A p air of enantiomers
(Erythreose)
H
CH2 OH
CH2 OH
(c)
(d)
A pair of en antiomers
(Threos e)
• Diastereomers: Stereoisomers that are not mirror images.
• (a)-(c) and (b)-(c), for example, are diastereomers.
15-20
Stereoisomers
Example: Mark all stereocenters in each molecule and tell
how many stereoisomers are possible for each.
OH
(a) CH2 =CHCHCH2 CH3
HO
(d)
HO
(b)
CH3
CH3
(e)
OH
(c)
NH2
OH
COOH
NH2
OH O
OH
OH
(f)
NH2
15-21
Stereoisomers
Example: Mark all stereocenters in each molecule and tell
how many stereoisomers are possible for each.
Solution:
OH
(a) CH2 =CHCHCH2 CH3
*
(b)
21 = 2
HO
NH2
HO
21 = 2
CH3
CH3
*
(c)
21 = 2
* COOH
(d)
OH O
OH
*
(e)
*
22 = 4
OH
* *
OH
NH2
22 = 4
* OH
(f)
* NH2
22 = 4
15-22
Stereoisomers
• The 2n rule applies equally well to molecules with three or
more stereocenters.
H
H3 C
H3 C
*
HO
*
*
*
*
* *
*
Cholesterol h as 8 stereocenters;
256 s tereoisomers are poss ible
H3 C
H
H
HO
H
H
H
Th is is th e stereoisomer found in
human metabolism
15-23
Optical Activity
• Ordinary light: Light waves vibrating in all planes
•
•
•
•
perpendicular to its direction of propagation.
Plane-polarized light: Light waves vibrating only in
parallel planes.
Polarimeter: An instrument for measuring the ability of a
compound to rotate the plane of plane-polarized light.
Optically active: Showing that a compound is capable
rotating the plane of plane-polarized light.
*NOTE: D,L will not be on this test (slides 24-26). The
designation is primarily used with carbs and amino acids,
so we will wait until that unit to cover it.
15-24
Polarimeter
Figure 15.6 Schematic diagram of a polarimeter with its
sample tube containing a solution of an optically active
compound.
15-25
Optical Activity
• Dextrorotatory: Clockwise rotation of the plane of
plane-polarized light. Indicated by (+).
• Levorotatory: Counterclockwise rotation of the plane of
plane-polarized light. Indicated by (-).
• Specific rotation: The observed rotation of an optically
active substance at a concentration of 1 g/mL in a
sample tube 10 cm long.
COOH
C
H
H3 C
OH
(S)-(+)-Lactic acid
21
[] D = +2.6°
COOH
H C
CH3
HO
(R)-(-)-Lactatic acid
21
[] D = -2.6°
15-26
Chirality of Biomolecules
Except for inorganic salts and a few low-molecular-weight
organic substances, the molecules in living systems, both
plant and animal, are chiral.
• Although these molecules can exist as a number of
stereoisomers, almost invariably only one
stereoisomer is found in nature.
• Instances do occur in which more than one
stereoisomer is found, but these rarely exist together in
the same biological system.
15-27
Chirality of Biomolecules
How an enzyme distinguishes between a molecule and its
enantiomer.
Figure 15.7 A schematic diagram of an enzyme surface
that can interact with (R)-glyceraldehyde at three binding
sites but with (S)-glyceraldehyde at only two of the three
sites.
15-28
Chirality of Biomolecules
Enzymes (protein biocatalysts) all have many
stereocenters.
• An example is chymotrypsin, an enzyme in the
intestines of animals that catalyzes the digestion of
proteins.
• Chymotrypsin has 251 stereocenters.
• The maximum number of stereoisomers possible is
2251!
• Only one of these stereoisomers is produced and used
by any given organism.
• Because enzymes are chiral substances, most either
produce or react with only substances that match their
stereochemical requirements.
15-29
Chirality of Biomolecules
• Because interactions between molecules in living
systems take place in a chiral environment, a molecule
and its enantiomer or one of its diastereomers elicit
different physiological responses.
• As we have seen, (S)-ibuprofen is active as a pain and
fever reliever, while its R enantiomer is inactive
(although the body can convert R to S, but it takes
time).
• The S enantiomer of naproxen is the active pain
reliever, but its R enantiomer is a liver toxin!
H3 C H
HOOC
(S)-Ib uprofen
H3 C H
HOOC
(S)-N aproxen
OCH3 15-30