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Chem
istry
A
CB C
D
A
CBC
D
CHAPTER 06 CHIRALITY: THE
HANDEDNESS OF MOLECULES
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
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Mirror images
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Chem
istry
Mirror images
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Chem
istry
A
CB C
D
A
CBC
D
CHAPTER 06 CHIRALITY: THE
HANDEDNESS OF MOLECULES
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Chem
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Stereoisomers
• Stereoisomers: Isomers (different compounds) that have all the same number and kind of atoms that are all connected the same, but differ in their arrangement in three dimensions.
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Chem
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ISOMERS
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ISOMERS(same number and kind of atoms, but are different molecules)
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Chem
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ISOMERS
17
ISOMERS(same number and kind of atoms, but are different molecules)
Constitutional(bonded differently)
Stereoisomers(Only different in 3-dimensional arrangement)
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Chem
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ISOMERS
17
ISOMERS(same number and kind of atoms, but are different molecules)
Constitutional(bonded differently)
Stereoisomers(Only different in 3-dimensional arrangement)
Enantiomers(mirror images)
Diastereomers(not mirror images)
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Chem
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ISOMERS
17
ISOMERS(same number and kind of atoms, but are different molecules)
Constitutional(bonded differently)
Stereoisomers(Only different in 3-dimensional arrangement)
Enantiomers(mirror images)
Diastereomers(not mirror images)
Configurational cis/trans
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Chem
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Symmetric Molecules
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Chem
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Chirality - Stereoisomers
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Chem
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Chirality - Stereoisomers
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Chem
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Chirality - Stereoisomers
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Chem
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Chirality - Stereoisomers
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Chem
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Chirality
• Enantiomers - molecules that are not superimposable on their mirror image.
• Molecules that can exist as enantiomers are called Chiral Molecules.
• Molecules that have a plane of symmetry are not chiral (achiral).
• Stereogenic Carbons are those that have four different groups attached.
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Chem
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Symmetry - Asymmetry
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Chem
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Biomolecules are Chiral
• Carbohydrates / Sugars
• DNA
• Amino Acids / Proteins
22
OH
HO
H
HO
H
HOHH OH
OH
Glucose
H2NO
OHR
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Chem
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Chirality in Smell and Taste
• Mirror image molecules (enantiomers) interact with chiral receptors in our nose differently.
23
O
(R)-(-)-Carvone (S)-(+)-Carvonespearmint oil caraway seed oil
O
(R)-(+)-Limonene (S)-(-)-Limoneneorange citrus turpentine/Lemon
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Chem
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Chiral Molecules in Enzymes
24
O
ONH
N
O
O
NOH
H
Me
HO
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Chem
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Chiral Molecules in Enzymes
24
O
ONH
N
O
O
NOH
H
Me
HO
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Chem
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Chiral Molecules in Enzymes
24
O
ONH
N
O
O
NOH
H
Me
HO
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Chem
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The Case of Thalidomide
25
(R)-thalidomidebeneficial sedative
NH
O O
N
O
O
*
stereogeniccarbon
(S)-thalidomideteratogencauses birth defects
NH
OO
N
O
O
*
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Chem
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The Case of Thalidomide
25
(R)-thalidomidebeneficial sedative
NH
O O
N
O
O
*
stereogeniccarbon
(S)-thalidomideteratogencauses birth defects
NH
OO
N
O
O
*
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Chem
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Optical Activity
• Enantiomers have identical physical properties
• mp, bp, spectroscopic, absorptions, etc.
• BUT they are different when interacting with plane-polarized light
• Christiaan Huygens - (1629-1695) Dutch astronomer, mathematician, andphysicist, discovers planepolarized light
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Chem
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Optical Activity
• Jean-Baptiste Biot (1774-1862)
• In 1815 he discovers that certain natural organic compounds rotate plane polarized light.
27
Historical perspectiveJean Baptiste Biot (1774-1862)
In 1815, he notes that certain
natural organic compounds (liquids
or solutions) rotate plane polarized
light (Optical Activity).
plane
polarized
light
tube containing
a liquid organic
compound or
solution
plane
polarized
light
IN OUTmoleculemolecule
moleculemolecule
molecule
molecule
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Chem
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Optical Activity
• Jean-Baptiste Biot (1774-1862)
• In 1815 he discovers that certain natural organic compounds rotate plane polarized light.
27
light travels in waves but oscillates in all three dimensions along the path of travel
polarizing filter
Light is polarized and oscillates in a single dimension
chiralsample
when the polarized light passes through a chiral sample, it is bent out of the original plane
chiralsampleenantiomer
Note that the enantiomer will bend the light in the opposite direction
Historical perspectiveJean Baptiste Biot (1774-1862)
In 1815, he notes that certain
natural organic compounds (liquids
or solutions) rotate plane polarized
light (Optical Activity).
plane
polarized
light
tube containing
a liquid organic
compound or
solution
plane
polarized
light
IN OUTmoleculemolecule
moleculemolecule
molecule
molecule
7
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Chem
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Tartaric Acid
• Carl Wilhelm Scheele (1742-1786)
• In 1769 he discovers Tartaric Acid fromtarter - the potassium salt of tartaric acidthat crystallizes out of wine.
28
Historical perspective
Carl Wilhelm Scheele (1742-1786)
“Oh, how happy I am! No care for eating or
drinking or dwelling, no care for my
pharmaceutical business, for this is mere play
to me. But to watch new phenomena this is all
my care, and how glad is the enquirer when
discovery rewards his diligence; then his heart
rejoices"
In 1769, he discovers Tartaric
Acid from tartar (the potassium
salt of tartaric acid, deposited
on barrels and corks during
fermentation of grape juice).
HO CO2H
CO2HHO
Tartaric Acid
6
*HO
O
OH
OHOH
O
*
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Chem
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Tartaric Acid
• Louis Pasteur - (1822-1895)
• In1849 he separated mirror image crystals of sodium ammonium tartrate.
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*O
O
OH
OHO
O
*Na NH4
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Chem
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Louis Pasteur
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“I found...that the tartrate was hemihedral..., but strange to say the paratartrate was hemihedral also. Only the hemihedral faces which in the tartrate were all turned the same way, were, in the paratartrates inclined sometimes to the right and sometimes to the left.... I carefully separated the crystals that were hemihedral to the right from those hemihedral to the left, and examined their solutions separately in the polarizing apparatus. I then saw with no less surprise than pleasure that the crystals hemihedral to the right deviated the plane of polarization to the right, and that those hemihedral to the left deviated it to theleft; and when I took an equal weightof each of the two kinds of crystals,the mixed solution was indifferenttowards the light in consequence of the neutralization of the two equal and opposite individual deviations.”
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Chem
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Optical Activity
• Amount of rotation depends on how many molecules the light interacts with.
• Light at 589 nm (Sodium D line)
• Standardized for unit cell and concentration
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observed rotation (°)cell length (dm) x conc. (g/mL)[α]D =
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Chem
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Racemates
• Racemic Mixture - 50/50 mixture of enantiomers. Shows NO optical activity.
32
“...when I took an equal weight of each of the two kinds of crystals, the mixed solution was indifferent towards the light in consequence of the neutralization of the two equal and opposite individual deviations.”
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Chem
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Racemates
• Racemic Mixture - 50/50 mixture of enantiomers. Shows NO optical activity.
32
“...when I took an equal weight of each of the two kinds of crystals, the mixed solution was indifferent towards the light in consequence of the neutralization of the two equal and opposite individual deviations.”
light travels in waves but oscillates in all three dimensions along the path of travel
polarizing filter
Light is polarized and oscillates in a single dimension
chiralsample
when the polarized light passes through a chiral sample, it is bent out of the original plane
chiralsampleenantiomer
Note that the enantiomer will bend the light in the opposite direction
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Chem
istry
CIP Rules for R & S Configuration
• Rectus - Right, Sinister - Left
33
ClCl
(R)-2-chlorobutane(S)-2-chlorobutane
1
23
HH 41
2 3
4
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Chem
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CIP Rules for R & S Configuration
• Rectus - Right, Sinister - Left
33
ClCl
(R)-2-chlorobutane(S)-2-chlorobutane
1
23
HH 41
2 3
4
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Chem
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R & S Configuration
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HONH2
OH sphingosine
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Chem
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R & S Configuration
34
HONH2
OH sphingosine
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Chem
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R & S Configuration
34
HONH2
OH sphingosine
HO RNH2
OH
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Chem
istry
R & S Configuration
35
H2N
CH3
O
OHNH O
OH
alanine proline
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Chem
istry
R & S Configuration
36
glucoseO
HO
HO
OHOH
OH
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Chem
istry
R & S Configuration
36
glucoseO
HO
HO
OHOH
OH
SR
SR
S
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Chem
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Diastereomers
• Diastereomers - stereoisomers that are not mirror images
37
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Chem
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Diastereomers
• Diastereomers - stereoisomers that are not mirror images
37
STEREOISOMERS
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Chem
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Diastereomers
• Diastereomers - stereoisomers that are not mirror images
37
STEREOISOMERS
ENANTIOMERS
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Chem
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Diastereomers
• Diastereomers - stereoisomers that are not mirror images
37
STEREOISOMERS
DIASTEREOMERS ENANTIOMERS
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Chem
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cis/trans Diastereomers
• Although not optically active (not chiral), cis/trans isomers are a form of diastereomer. They differ only in their arrangement in 3-dimensions but are not mirror images.
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Chem
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configurational Diastereomers
39
OH
OH
O
HO
O
HO
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Chem
istry
configurational Diastereomers
39
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
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Chem
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configurational Diastereomers
39
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
S R
S R
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Chem
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configurational Diastereomers
39
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
ENANTIOMERS
S R
S R
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Chem
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configurational Diastereomers
39
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
ENANTIOMERS
S R
S R
OH
OH
O
HO
O
HOS
R
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Chem
istry
configurational Diastereomers
39
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
ENANTIOMERS
S R
S R
DIASTEREOMERSDIASTEREOMERS
OH
OH
O
HO
O
HOS
R
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Chem
istry
MESO compounds
• Meso Compounds are molecules that contain stereogenic carbons, but are not chiral. Their mirror images are identical. This occurs when there is a plane of symmetry in the molecule.
40
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
S R
SR
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Chem
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MESO compounds
• Meso Compounds are molecules that contain stereogenic carbons, but are not chiral. Their mirror images are identical. This occurs when there is a plane of symmetry in the molecule.
40
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
S R
SR
IDENTICAL
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Chem
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MESO compounds
• Meso Compounds are molecules that contain stereogenic carbons, but are not chiral. Their mirror images are identical. This occurs when there is a plane of symmetry in the molecule.
40
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
S R
SR
IDENTICAL
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Fischer Projections
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Chem
istry
Fischer Projections
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Chem
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Diasteromers
• Diastereomers have different physical properties
43
OH
OH
O
HO
O
HO
HO
HO
O
OH
O
OH
OH
OH
O
HO
O
HO
(S,S) +12° 168-170°C 1.7598
(R,R) -12° 168-170°C 1.7598
(S,R) meso 0 146-148°C 1.666
molecule configoptical
rotation densitymp
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Chem
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ISOMERS
44
ISOMERS(same number and kind of atoms, but are different molecules)
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Chem
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ISOMERS
44
ISOMERS(same number and kind of atoms, but are different molecules)
Constitutional(bonded differently)
Stereoisomers(Only different in 3-dimensional arrangement)
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Chem
istry
ISOMERS
44
ISOMERS(same number and kind of atoms, but are different molecules)
Constitutional(bonded differently)
Stereoisomers(Only different in 3-dimensional arrangement)
Enantiomers(mirror images)
Diastereomers(not mirror images)
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Chem
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ISOMERS
44
ISOMERS(same number and kind of atoms, but are different molecules)
Constitutional(bonded differently)
Stereoisomers(Only different in 3-dimensional arrangement)
Enantiomers(mirror images)
Diastereomers(not mirror images)
Configurational cis/trans
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Chem
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Reactions can produce stereogenic centers
• Racemic mixtures will always result unless there is other chirality to influence a difference in the reaction path.
45
HBr Br
Br Br+
R S
50:50
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Chem
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Chirality in Reactions
46
Br2
Br
BrBr
Br Br
Br
+
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Chem
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Chirality in Reactions
47
cis-2-butene
Br2
Br Br BrBr
+ enantiomersRS S R
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Chem
istry
Chirality in Reactions
47
cis-2-butene
Br2
Br Br BrBr
+ enantiomersRS S R
Br
Br
Br
BrS
SR
R
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Chem
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Chirality in Reactions
48
trans-2-butene
Br2
Br Br BrBr
Br
Br
Br
Br
+ identical
MESO
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Chem
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Diastereoselectivity
• An existing stereogenic center can influence the creation of another.
49
Br
Br
Br2
Br
BrBr
Br
H3C
H3C
H3C
Major Product
H3C
BrH3C
Major Product
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Chem
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Resolution of Enantiomers
• The separation of enantiomers from a racemic mixture is called a resolution.
50
*O
O
OH
OHO
O
*Na NH4
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Chem
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Chemical Resolution
• Enantiomers have identical physical properties, so we need to prepare diastereomers.
51
R
S
SO
OHOH
O
OHOH
+
NH2
racemicmixture
one enantiomer
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Chem
istry
Chemical Resolution
• Enantiomers have identical physical properties, so we need to prepare diastereomers.
51
R
S
SO
OHOH
O
OHOH
+
NH2
racemicmixture
one enantiomer
O
OOH NH3
+
O
OOH NH3
diastereomeric salts
R S
S S
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Chem
istry
Chemical Resolution
• We can also make covalent bonds.
52
O
Cl+
NH2
one enantiomer diastereomeric products
NH2
Racemic Mixture
HN
O
Ph
HN
O
PhR
S
S
S
S
S
R
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Chem
istry
Indication of mixed stereochemistry
53
NH2
Racemic Mixture
Recommended