Transcript Slide 1
Chirality
Chirality - the Handedness
of Molecules
Isomers
we concentrate on enantiomers and diastereomers
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
CH2 CH3
Origin al molecu le
HO
H C CH
3
CH3 CH2
Mirror image
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
H3 C
C CH CH
2
3
H
The mirror image
rotated b y 180°
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 not superposable
they are different molecules
nonsuperposable mirror images are enantiomers
Enantiomers
Objects that are not superposable 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
Enantiomers
If an object and its mirror image are
superposable, they are identical and there is no
possibility of enantiomerism
such an object is achiral (without chirality)
An achiral molecule, consider 2-propanol
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
Enantiomers
to see the relationship between the original and its
mirror image, rotate the mirror image by 120°
OH
C H
H3 C
CH 3
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°
after this rotation, we see that all atoms and bonds of
the mirror image fit exactly on the original
the original and its mirror image are the same
Enantiomers
To summarize
an object that is nonsuperposable on its mirror image is chiral
(it shows 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
an object that is superposable on its mirror image is achiral
(without chirality)
nonsuperposable mirror images are called enantiomers
enantiomers, like gloves, always come in pairs
Drawing Enantiomers
Following are four different representations for one of the
enantiomers of 2-butanol
OH
C H
H3 C
CH2 CH3
(1)
H
H3 C
OH
C
CH2 CH3
(2)
H OH
OH
(3)
(4)
both (1) and (2) show all four groups bonded to the
stereocenter and show the tetrahedral geometry
(3) is a more abbreviated line-angle formula; although we
show the H here, we do not normally show them in line-angle
formulas
(4) is the most abbreviated representation; you must
remember that there is an H present on the stereocenter
Drawing Mirror Images
on the left is one enantiomer of 2-butanol
on the right are two representations for its mirror image
(in this case, its enantiomer)
OH
One en antiomer
of 2-b utanol
OH
OH
Alternative rep res entations
for its mirror image
The R,S System
To assign an R or S configuration
assign a priority from 1 (highest) to 4 (lowest) to each
group on the stereocenter;
orient the stereocenter so that the group of lowest
priority is facing away from you
read the three groups projecting toward you in order
from (1) to (3)
if reading the groups is clockwise, the configuration is R
(Latin, rectus, straight, correct)
if reading the groups is counterclockwise, the
configuration is S (Latin: sinister, left)
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
Atom or
Grou p
-I
-Br
-Cl
-SH
-OH
-NH2
O
-COH
O
-CNH2
O
-CH
-CH2 OH
-CH2 NH2
-CH2 CH3
-CH2 H
-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)
The R,S System
Example: assign priorities to the groups in each set
(a) -CH2 OH and -CH2 CH2 OH
O
(c) -CH2 OH and -CH2 CH2 COH
(b) -CH2 CH2 OH and -CH2 NH2
(d) -CH2 NH2
O
and -CH2 COH
The R,S System
Example: assign priorities to the groups in each set
(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
(d) -CH2 NH2
O
and -CH2 COH
O
-CH2 NH2
-CH2 COH
Higher priority Low er priority
The R,S System
example: assign an R or S configuration to each
stereocenter
OH
(a)
C
H
H3 C
CH2 CH3
2-Bu tanol
H2 N H
(b)
C
H3 C
COOH
Alanin e
The R,S System
example: assign an R or S configuration to each
stereocenter
1
(a)
3
H3 C
OH
C
4
R
H
CH2 CH3
2
(R)-2-Butan ol
R
1
4
H2 N H
(b)
R
C 2
H3 C
COOH
3
(R)-Alanine
R
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 in active enantiomer
of ib uprofen
H3 C H
HOOC
The active enan tiomer
the R,S system is a way to distinguish between enantiomers
without having to draw them and point to one or the other
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)
Chirality in Biomolecules
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
the S enantiomer of naproxen is the active pain
reliever, but its R enantiomer is a liver toxin!
H3 C H
HOOC
H3 C H
HOOC
OCH3
(S)-Ib uprofen
(S)-N aproxen
Stereocenters
A molecule with n stereocenters has a maximum
number of 2n stereoisomers
a molecule with one stereocenter, 21 = 2 stereoisomers
(enantiomers) are possible
for a molecule with two stereocenters, a maximum of 22
= 4 stereoisomers (two pair of enantiomers)
for a molecule with three stereocenters, a maximum of
23 = 8 stereoisomers (four pairs of enantiomers) is
possible
and so forth
Fischer Projection Formulas
Fischer Projection: show configuration of chiral
molecules in two-dimensional representation
Vertical bonds are directed away
Horizontal bonds are directed toward you
OH
H
H3CH2C
H
OH
CH2CH3
H
OH
CH2CH3
Enantiomers & Diastereomers
2,3,4-Trihydroxybutanal
O
* *
HOCH2 -CH-CH-CH
OH OH
two stereocenters; 22 = 4 stereoisomers exist
Two Stereocenters
2,3,4-trihydroxybutanal
CHO
CHO
H
C
OH HO
C
H
H
C
OH HO
C
H
CH2 OH
CH2 OH
(a)
(b)
A p air of enantiomers
(Erythreose)
CHO
CHO
H
C
OH HO
C
H
HO
C
H
C
OH
H
CH2 OH
CH2 OH
(c)
(d)
A pair of en antiomers
(Threos e)
diastereomers: stereoisomers that are not mirror images
(a) and (c), for example, are diastereomers
Meso Compounds
Meso compound: an achiral compound possessing two or
more stereocenters
tartaric acid
two stereocenters; 2n = 4, but only three stereoisomers exist
COOH
COOH
H
C
OH HO
C
H
H
C
OH HO
C
H
COOH
COOH
A meso compound
(plane of symmetry)
COOH
COOH
H
C
OH HO
C
H
HO
C
H
C
OH
COOH
H
COOH
A pair of enantiomers
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
Stereoisomers
example: mark all stereocenters in each molecule and
tell how many stereoisomers are possible for each
solution:
OH
(a) CH2 =CHCHCH2 CH3
*
21 = 2
HO
* COOH
HO
NH2
(d)
21 = 2
OH O
OH
(b)
CH3
CH3
21 = 2
*
*
(e)
*
22 = 4
(c)
OH
* *
OH
NH2
2
2 =4
* OH
(f)
* NH2
22 = 4
Three Or More Stereocenters
how many stereocenters are present in the molecule on
the left?
how many stereoisomers are possible?
one of the possible stereoisomers is menthol
assign an R or S configuration to each stereocenter in
menthol
OH
2-Is op ropyl-5-meth ylcyclohexanol
OH
Menthol
Three Or More Stereocenters
R
*
*
*
OH
2-Is op ropyl-5-meth ylcyclohexanol
23 = 8 possible stereoisomers
S
R
OH
Menthol
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