Download - Stereochemistry
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Stereochemistry
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Isomer OrganizationIsomersIsomers
StereoisomersStereoisomers Constitutional isomersConstitutional isomers
GeometricCis/trans
GeometricCis/trans
Conformational Isomers
Conformational Isomers
EnantiomersEnantiomers DiastereomersDiastereomers
Meso compounds
Meso compounds
EpimersEpimers
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Stereoisomers
• Same bonding sequence.• Different arrangement in space.• Example: HOOC-CH=CH-COOH
has two geometric (cis-trans) isomers
CHO
O
CH
CH
C
O
OH
fumaric acid, mp 287 C essential metabolite
o
HC
CC
H
C
O
OH
O
HO
maleic acid, mp 138 C toxic irritant
o
=>
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Chirality• “Handedness”: right glove doesn’t fit the left
hand.• Mirror-image object is different from the
original object
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Examples of Handed Objects
• Your hands, from the previous slide• Gloves• Scissors• Screws• Golf clubs
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How about molecules?• Chemical substances can be handed• Handed substances are said to be chiral• Molecules, that are chiral are
nonsuperimposable on their mirror image
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Chirality in Molecules
• cis isomers are achiral (not chiral).
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Chirality in Molecules
• The cis isomer is achiral.• The trans isomer is chiral.
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Chirality in Molecules
• The cis isomer is achiral.• The trans isomer is chiral.• Enantiomers: nonsuperimposable mirror
images, different molecules.
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Chirality in Molecules
• The cis isomer is achiral.• The trans isomer is chiral.• Enantiomers: nonsuperimposable mirror
images, different molecules.• One enantiomeric form of limonene smells
like oranges, while its mirror image smells like lemons.
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Chirality in Molecules• The cis isomer is achiral.• The trans isomer is chiral.• Enantiomers: nonsuperimposable mirror images,
different molecules.• One enantiomeric form of limonene smells like
oranges, while its mirror image smells like lemons.• The one enantiomer of carvone is the essence of
caraway, and the other, the essence of spearmint.• Most molecules in the plant and animal world are
chiral and usually only one form of then enantiomer is found.
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Chirality in Molecules• The cis isomer is achiral.• The trans isomer is chiral.• Enantiomers: nonsuperimposable mirror images,
different molecules.• One enantiomeric form of limonene smells like
oranges, while its mirror image smells like lemons.• The one enantiomer of carvone is the essence of
caraway, and the other, the essence of spearmint.• Most molecules in the plant and animal world are
chiral and usually only one form of then enantiomer is found.
• Nineteen of the twenty known amino acids are chiral, and all of them are classified as left handed.
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Chirality in Molecules• The cis isomer is achiral.• The trans isomer is chiral.• Enantiomers: nonsuperimposable mirror
images, different molecules.
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Stereocenters• Any atom at which the exchange of two
groups yields a stereoisomer.• Examples:
• Asymmetric carbons• Double-bonded carbons in cis-trans isomers
=>
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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.
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Absolute Configuration
• Called the Cahn-Ingold-Prelog convention• 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).
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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.
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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)
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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
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Plane-Polarized Light
• Polarizing filter – calcite crystals or plastic sheet.
• When two filters are used, the amount of light transmitted depends on the angle of the axes.
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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)
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Biological Discrimination
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Racemic Mixtures
• Equal quantities of d- and l- enantiomers a 50/50 mixture.
• Notation: (d,l) or ()• No optical activity.• The mixture may have different b.p. and m.p.
from the enantiomers!
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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.
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Fischer Rules• Carbon chain is on the vertical line.• Horizontal bonds pointing up with respect to the
plane of the paper.• Vertical bonds pointing down with respect to the
plane of the paper.• 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!
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Fischer Structures
• 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
=>
A meso compound
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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)
Mirror image, both would be R
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Diastereomers
• Stereoisomers that are not mirror images.• Molecules with 2 or more chiral carbons.• Geometric isomers (cis-trans), since they are
not mirror images.
C CH H
CH3H3C
cis-2-butene trans-2-butene
C CH
H3C
CH3
H
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Ring Compounds
• Cis-trans isomers possible.• May also have enantiomers.• Example: trans-1,2-dimethylcyclopentane
=>
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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.
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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
enantiomers
A meso compound, contains 2 or more stereocenters and a plane of symmetry
*
*
*
*
*
*
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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, we now know absolute configurations: D is (R) and L is (S).
• No relationship to dextro- or levorotatory, meaning that some D enantiomers are (R) and some are (S).
• Anyone who can look at a structure and determine which way it will rotate polarized light receives an automatic Noble Prize! There is a lot we do not know!
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D and L Assignments
CHO
H OH
CH2OH
D-(+)-glyceraldehyde
COOH
H2N H
CH2CH2COOH
L-(+)-glutamic acid
*
Penultimate carbon is the stereocenter farthest away from the carbonyl group. If the higher priority group is on the left, then (L), if on the right then (D) sugar.
CHO
H OH
HO H
H OH
H OH
CH2OHD-(+)-glucose
*
*
*
*
*
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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
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Resolution of Enantiomers
• Pasteur was the first to resolve an enatiomeric mixture, using a magnifying glass and tweezers.
• Animals can consume a racemate and metabolize on of the tow enantiomers, while the other is recovered in their waste products.
• Chemical means, described on the next slide
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Chemical Resolution of Racemate• React a racemic mixture with a chiral
compound to form diastereomers, which can
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End Stereochemistry