Chirality Identifying stereocenters R and S nomenclature Enantiomers Racemic mixtures meso compounds

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Chirality Identifying stereocenters (R) and (S)
nomenclature Enantiomers Racemic
mixtures meso compounds Diastereomers Cyclic
alkanes Optical activities (you must be able to
do calculations) specific rotation enantiomeric
excess, optical purity. Absolute
configurationsFischer Projections Resolution of
Enantiomers
Chapter 5, Stereochemistry
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Stereoisomers

• Same bonding sequence (i.e., NOT constitution
  isomers)
• Different arrangement in space
• Example HOOC-CHCH-COOHhas two geometric
  (cis-trans) isomers

A. Chirality

• Handedness right glove doesnt fit the left
  hand.
• Mirror-image object is different from the
  original object.
• A molecule is chiral if it is not superimposable
  with its mirror image.
• If they are superimposable, it is achiral.

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Chirality in Molecules

• The cis isomer of a cyclic alkane is achiral.
• The trans isomer is chiral.
• Enantiomers two chiral molecules having the
  relationship of mirror image of each other are
  enantiomers.
• This is one of the central topics of this chapter.

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Stereocenters (also called chiral atoms or
asymmetric atoms)

• Any atom at which the exchange of two groups
  yields a stereoisomer. It is often designated by
  a .
• A carbon atom is a stereocenter if it has four
  different substituents attached.

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Carbon stereocenters (yes, again)

• Tetrahedral carbons with 4 different attached
  groups are stereocenters or chiral carbon atoms.
• If theres only one chiral carbon in
• a molecule, its mirror image will be a
• different compound, and
• they are enantiomers.
  

Mirror Planes of Symmetry

• If two groups are the same,
• the carbon is achiral.
• A molecule with an internal
• mirror plane cannot be chiral.

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Biological Discrimination
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B. Properties of Enantiomers

• Same boiling point, melting point, density
• Same refractive index
• Different direction of rotation in polarimeter
• Different interactions with other chiral
  molecules
• Enzymes
• Taste buds, scent

B.1. Plane-Polarized Light
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Polarimetry

• Use monochromatic light, usually sodium D (l
  5996 nm)
• Movable polarizing filter to measure angle
• Clockwise dextrorotatory d or ()
  Counterclockwise levorotatory l or (-)
• Not related to (R) and (S)
  
  
  

B.2. Specific rotation
? (observed)
Observed rotation depends on the length of the
cell and concentration, temperature, and
wavelength of light.
c is concentration in g/mL l is length of path in
decimeters.
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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.

Length in decimeter
Concentration in g/mL.
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B.3. Absolute structure

• enantiomers give the same amount of rotation,
  but to the opposite directions.
• 2-butanol ?D25 13.52o, rotate light
  clockwise
• ?D25 -13.52o, rotate light
  counterclockwise
• There is no direct relationship between absolute
  structure of a compound and the direction of
  polarized light rotation.
• There is no relationship between (R) or (S) and
  () or (-).

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Racemic Products

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

gt
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B.4. Racemic Mixtures

• Equal quantities of d- and l-enantiomers,
  Notation (d,l) or (?)
• E.g., (?)-2-butanol.
• The net optical rotation 0.
• The mixture may have different b.p. and m.p. from
  the enantiomers!
• A racemate can crystallize in several ways.
• Separate () and (-) (Pastor separation of
  tartaric acid)
• Racemic crystal gt only one type of crystal of
  equal amount of d and l forms.

B.5. Measure
Enantiomeric excess (ee) Amount of pure
enantiomer in excess of the racemic mixture.
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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?.
Let x be the mole of (R), and (1-x) be the mole
of (S)
2x -1 0.2 2x 0.2 1 1.2 x 1.2/2 0.6
60 gt composition of the R
enantiomer (1-x) 1 0.6 0.4 40 gt
composition of the S enantiomer
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C. Assign (R) or (S), Nomenclature of
stereocenters

• Assign priority, according to the
  Cahn-Ingold-Prelog rules, to the 4 substituents
  on the stereocenter, in order of (1) gt (2) gt (3)
  gt (4).
• Arrange the molecule so that the lowest priority
  group, (4), is in the back, and then draw a
  Newman projection looking along the bond from the
  stereocenter C down to (4).
• Draw a circular arrow from highest (1) through
  (2) to the third priority group (3).
• Clockwise arrow, assign R to the stereocenter.
• Counterclockwise arrow, assign S to the
  stereocenter.

(1)
(2)
(3)
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Priority assignment Cahn-Ingold-Prelog Rules

• The higher atomic number has a higher priority
  than the lower one.
• e.g., Br gt Cl gt F gt O gt N gt C gt H
• The higher mass isotope has higher priority than
  the lower mass.
• e.g., T gt D gt H
• For the same atoms directly attached to the
  stereocenter, move along the two chains until a
  point of difference, and use the above priority
  rules to determine which group has higher
  priority.
• Double (triple) bonds are treated by assuming
  that each such bonded atoms is duplicated
  (triplicated).

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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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D.1. Diastereomers compounds with more than 1
stereocenter

• Stereoisomers that are not mirror images are
  diastereomers.
• For a compound with 2 stereocenters gt 4 stereo
  isomers.
• Consider 2-chloro-3-iodobutane,
  CH3-CHCl-CHI-CH3

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D.2 Meso compounds there is a plane of
symmetry or a centerof symmetry within the
molecule.
Consider CH3CHCl-CHClCH3
Maximum number is 2n, where n the number
of chiral carbons.
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Ring Compounds
Alkenes
Cis-trans isomers are not mirror images, so these
are diastereomers.

• Cis-trans isomers possible.
• May also have enantiomers.
• Example trans-1,2-dimethylcyclopentane.

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D.3. Nonmobile Conformers

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

• 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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D. 4. 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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E. Resolution of Enantiomers

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

gt
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F. 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.

Carbon chain is on the vertical line. Highest
oxidized carbon at top. Rotation of 180? in plane
doesnt change molecule. Do not rotate 90?!
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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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G. Stereo-representation of cyclic compounds

• 1,4-dimethylcyclohexane (no stereocenter)
• 1,3-dimethylcyclohexane (2 stereocenters, up to 4
  stereoisomers)
• 1,2-dimethylcyclohexane (2 stereocenters, up to 4
  stereoisomers)