Stereochemistry
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Transcript of Stereochemistry
Chapter 5Stereochemistry
Organic Chemistry
Chapter 5 2
Chirality• “Handedness”: right glove doesn’t fit the
left hand.• Mirror-image object is different from the
original object. =>
Chapter 5 3
Stereoisomers• Geometric isomers: cis-trans isomers.• Enantiomers: nonsuperimposable mirror
images, different molecules. =>
cis-1,2-dichlorocyclopentane trans -1,2-dichlorocyclopentane
H
ClH
ClH
ClH
ClH
ClCl
HH
ClCl
H
Chapter 5 4
Chiral Carbons• Tetrahedral carbons with 4 different
attached groups are chiral.• Its mirror image will be a different
compound (enantiomer). =>
Chapter 5 5
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 5 6
(R), (S) Nomenclature
• 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).
C
CO OH
H3C NH2H
natural alanine=>
Chapter 5 7
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 5 8
Assign Priorities
C
CO OH
H3C NH2H
natural alanine1
2
3 4
Cl
HCl
H*
12
34
12
3
4
=>
CC
O
H
CH CH2
CH2OHCH(CH3)2
* CC
C
CH2OHCH(CH3)2
H O
O
C
CH CH2
C
*expands to
Chapter 5 9
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 5 10
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 5 11
Optical Activity• Rotation of plane-polarized light• Enantiomers rotate light in opposite directions,
but same number of degrees.
=>
Chapter 5 12
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 5 13
Specific RotationObserved rotation depends on the length
of the cell and concentration, as well as the strength of optical activity, temperature, and wavelength of light.
[] = (observed) c l
c is concentration in g/mLl is length of path in decimeters. =>
Chapter 5 14
Calculate []D
• A 1.00-g sample is dissolved in 20.0 mL ethanol. 5.00 mL of this solution is placed in a 20.0-cm polarimeter tube at 25C. The observed rotation is 1.25 counterclockwise.
=>
Chapter 5 15
Biological Discrimination
=>
Chapter 5 16
Racemic Mixtures
• Equal quantities of d- and l- enantiomers.• Notation: (d,l) or ()• No optical activity.• The mixture may have different b.p. and m.p.
from the enantiomers!
=>
Chapter 5 17
Racemic ProductsIf optically inactive reagents combine to
form a chiral molecule, a racemic mixture of enantiomers is formed.
=>
Chapter 5 18
Optical Purity
• Also called enantiomeric excess.• Amount of pure enantiomer in excess of
the racemic mixture.• If o.p. = 50%, then the observed rotation
will be only 50% of the rotation of the pure enantiomer.
• Mixture composition would be 75-25. =>
Chapter 5 19
Calculate % Composition
The specific rotation of (S)-2-iodobutane is +15.90. Determine the % composition of a mixture of (R)- and (S)-2-iodobutane if the specific rotation of the mixture is -3.18.
=>
Chapter 5 20
Chirality of Conformers
• If equilibrium exists between two chiral conformers, molecule is not chiral.
• Judge chirality by looking at the most symmetrical conformer.
• Cyclohexane can be considered to be planar, on average.
=>
Chapter 5 21
Mobile ConformersH
BrH
Br
H
BrH
Br
Nonsuperimposable mirror images,but equal energy and interconvertible.
BrBr
H H
Use planarapproximation.
=>
Chapter 5 22
Nonmobile ConformersIf the conformer is sterically hindered, it
may exist as enantiomers.
=>
Chapter 5 23
Allenes• Chiral compounds with no chiral carbon• Contains sp hybridized carbon with
adjacent double bonds: -C=C=C-• End carbons must have different groups.
Allene is achiral. =>
Chapter 5 24
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 5 25
Fischer Rules
• Carbon chain is on the vertical line.• 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 5 26
Fischer Mirror Images
• Easy to draw, easy to find enantiomers, easy to find internal mirror planes.
• Examples:CH3
H Cl
Cl H
CH3
CH3
Cl H
H Cl
CH3
CH3
H Cl
H Cl
CH3=>
Chapter 5 27
Fischer (R) and (S)• Lowest priority (usually H) comes forward, so
assignment rules are backwards!• Clockwise 1-2-3 is (S) and counterclockwise
1-2-3 is (R).• Example:
CH3
H Cl
Cl H
CH3
(S)
(S) =>
Chapter 5 28
Diastereomers
• Stereoisomers that are not mirror images.• Geometric isomers (cis-trans)• Molecules with 2 or more chiral carbons.
=>
Chapter 5 29
Alkenes
Cis-trans isomers are not mirror images, so these are diastereomers.
C CH H
CH3H3Ccis-2-butene trans-2-butene
C CH
H3C
CH3
H =>
Chapter 5 30
Ring Compounds
• Cis-trans isomers possible.• May also have enantiomers.• Example: trans-1,3-dimethylcylohexane
CH3
H
H
CH3
CH3
H
H
CH3
=>
Chapter 5 31
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 5 32
ExamplesCOOH
H OH
HO H
COOH
(2R,3R)-tartaric acid
COOH
COOH
HO H
H OH
(2S,3S)-tartaric acid
=> (2R,3S)-tartaric acid
COOH
COOH
H OH
H OH
Chapter 5 33
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, now know absolute configurations: D is (R) and L is (S).
• No relationship to dextro- or levorotatory. =>
Chapter 5 34
D and L AssignmentsCHO
H OH
CH2OH
D-(+)-glyceraldehyde
*CHO
H OH
HO H
H OH
H OH
CH2OHD-(+)-glucose
*
COOH
H2N H
CH2CH2COOH
L-(+)-glutamic acid
*=>
Chapter 5 35
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 5 36
Resolution of EnantiomersReact a racemic mixture with a chiral compound to
form diastereomers, which can be separated.
=>
Chapter 5 37
ChromatographicResolution of Enantiomers
=>
Chapter 5 38
End of Chapter 5