Properties of Chiral Molecules: Optical Activity

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Properties of Chiral MoleculesOptical Activity
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Biological Discrimination
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Optical Activity

• A substance is optically active if it rotates
  the plane of polarized light.
• In order for a substance to exhibit
  opticalactivity, it must be chiral and one
  enantiomer must be present in excess of the
  other.

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Light

• optical activity is usually measured using light
  having a wavelength of 589 nm
• this is the wavelength of the yellow light from
  a sodium lamp and is called the D line of sodium

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Polarized light

• ordinary (nonpolarized) light consists of
  many beams vibrating in different planes
• plane-polarized light consists of only those
  beams that vibrate in the same plane

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Polarization of light
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Rotation of plane-polarized light
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Rotation of plane-polarized light
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Polarimetry

• Use monochromatic light, usually sodium D
• Movable polarizing filter to measure angle
• Enantiomers rotate light in opposite directions,
  but same number of degrees.
• Clockwise dextrorotatory d or ()
• Counterclockwise levorotatory l or (-)
• Not related to (R) and (S)
  
  
  

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Specific rotation

• observed rotation (a) depends on the number of
  molecules encountered and is proportional
  to path length (l), and concentration (c)
• therefore, define specific rotation a as

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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 25?C. The observed rotation
  is 1.25? counterclockwise.
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Racemic Products

• If optically inactive reagents combine to form a
  chiral molecule, a racemic mixture of enantiomers
  is formed.

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a sample that is optically inactive can beeither
an achiral substance or a racemicmixture
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Optical Purity

• Also called enantiomeric excess (ee).
• 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.
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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?.

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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.
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Mobile Conformers
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Nonmobile Conformers

• If the conformer is sterically hindered, it may
  exist as enantiomers.

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Allenes

• Chiral compounds with no chiral carbon
• Contains sp hybridized carbon with adjacent
  double bonds -CCC-
• End carbons must have different groups.

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Fischer Projections
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Fischer Guidelines

• Fischer formulas only have meaning for structures
  with stereo centers
• Fischer formulas may only be rotated 180o in the
  plane of the paper
• Any even number of exchange of groups around a
  stereocenter produces the original configuration
• If manipulation outlined in 2 or 3 allows one
  Fischer projection to superimpose on another,
  they are the same steroisomer
• Any one exchange of groups around a stereocenter
  produces the other stereoisomer (R? S, S? R)

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Fischer Projections

• recall for Fischer projection horizontal bonds
  point toward you vertical bonds point away
• staggered conformation does not have correct
  orientation of bonds for Fischer projection

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Fischer projections

• transform molecule to eclipsed conformation in
  order to construct Fischer projection

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2,3-Butanediol
3
2

• Consider a molecule with two equivalently
  substituted stereogenic centers such as
  2,3-butanediol.

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Three stereoisomers of 2,3-butanediol
2R,3R
2S,3S
2R,3S
chiral
chiral
achiral
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Three stereoisomers of 2,3-butanediol
2R,3R
2S,3S
2R,3S
chiral
chiral
achiral
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Three stereoisomers of 2,3-butanediol
these two areenantiomers
2R,3R
2S,3S
chiral
chiral
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Three stereoisomers of 2,3-butanediol
these two areenantiomers Mirror Plane Rotate
180o
2R,3R
2S,3S
chiral
chiral
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Three stereoisomers of 2,3-butanediol
2R,3S
the third structure is superposable on its mirror
image (rotate 180o)
achiral
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Three stereoisomers of 2,3-butanediol
CH3

• therefore, this structure and its mirror image
  are the same
• it is called a meso form
• a meso form is an achiral molecule that has
  stereogenic centers

H
HO
H
HO
CH3
2R,3S
achiral
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Three stereoisomers of 2,3-butanediol

• meso forms have a plane of symmetry and/or a
  center of symmetry
• plane of symmetry is most common case
• top half of molecule is mirror image of bottom
  half

2R,3S
achiral
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Three stereoisomers of 2,3-butanediol
A line downthe center ofthe Fischer projection
of ameso formbisects it intotwo mirror-image
halves.
2R,3S
achiral
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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

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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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Examples
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AbsoluteandRelative Configuration
R, S convention is ABSOLUTE
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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, now know absolute
  configurations D is (R) and L is (S).
• No relationship to dextro- or levorotatory.
  
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D and L Assignments



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Configuration

• Relative configuration compares the arrangement
  of atoms in space of one compound with those of
  another.
• Absolute configuration is the precise
  arrangement of atoms in space.

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Relative configuration
Pd, H2
a 33.2
a 13.5

• No bonds are made or broken at the stereogenic
  centerin this experiment. Therefore, when
  ()-3-buten-2-ol and ()-2-butanol have the same
  sign of rotation, the arrangement of atoms in
  space is analogous. The twohave the same
  relative configuration.

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Two possibilities

H2, Pd
H2, Pd

• But in the absence of additional information, we
  can't tell which structure corresponds
  to()-3-buten-2-ol, and which one to
  ()-3-buten-2-ol.

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Two possibilities

H2, Pd
H2, Pd

• Nor can we tell which structure corresponds
  to()-2-butanol, and which one to ()-2-butanol.

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Absolute configurations

H2, Pd
a 33.2
a 13.5
H2, Pd
a 13.5
a 33.2
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Relative configuration
HBr
a -5.8
a 4.0

• Not all compounds that have the same
  relativeconfiguration have the same sign of
  rotation. No bondsare made or broken at the
  stereogenic center in thereaction shown, so the
  relative positions of the atoms are the same.
  Yet the sign of rotation changes.

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Resolution of Enantiomers

• React a racemic mixture with a chiral compound to
  form diastereomers, which can be separated.

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Strategy
enantiomers
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Strategy
enantiomers
2R()
diastereomers
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Strategy
enantiomers
C()R()
2R()
C(-)R()
diastereomers
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Strategy
C()
enantiomers
R()
C()R()
2R()
C(-)R()
R()
diastereomers
C(-)
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ChromatographicResolution of Enantiomers
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