Enantiomers

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Enantiomers

• Enantiomers Isomers which are not
  superimposable on their mirror image
• Enantiomers are related to each other as a right
  hand is related to your left hand

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Enantiomers (cont.)

• Enantiomers usually (but not always) result when
  a tetrahedral carbon atom has four different
  substituents around it (e.g. CHXYZ) in which
  X,Y, and Z constitute different substituents

3
Chirality

• Isomers that exist in two enantiomeric forms are
  said to be chiral (comes from the Greek work
  hand)
• Compounds that are chiral lack a plane of
  symmetry (i.e., one half of the molecule is not a
  mirror image of the other half)

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Chirality (cont.)

• A molecule that has a plane of symmetry in the
  molecule is said to be achiral (not chiral)
• A carbon atom that has four different
  substituents attached to it called a chiral
  carbon. Also known as a chiral center ,
  stereogenic center, or an asymmetric center

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Sequence Rules for Specifying Configuration

• Configurations for optically active isomers are
  assigned either an R (rectus) or an S (sinister)

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Sequence Rules for Assigning R, S Configuration

• Priority is given to the substituent atom
  directly attached to the chiral carbon which has
  the highest atomic number.

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Sequence Rules (cont.)

• Double or triple bonds are treated as if they had
  duplicate or triplicate single bonds
• Once priority is assigned, then stereochemical
  configuration (R or S) can be assigned.

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Sequence Rules (cont.)

• If a decision cannot be reached based on the
  above rule then second atoms of each substituent
  are compared, continuing on if necessary until an
  atom of higher atomic number is reached

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Assigning R and S Configuration

• When assigning R,S configuration, use the
  steering wheel approach
• The lowest priority group is placed in the rear
  of the molecule. This should act like a
  steering wheel column
• The remaining groups are placed in a manner that
  they serve as spokes on the wheel.

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Assigning R and S Configuration(cont.)

• Count the substituents by decreasing priority
  (decreasing rank). If the decrease occurs in a
  clockwise direction (to the right, as in the hand
  of a clock), then the configuration is assigned a
  R, if the decrease occurs in a counterclockwise
  direction, then the configuration is assigned an S

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Assigning R and S configuration (cont.)

• Important note The R and S configuration and
  the sign of rotation () or (-) are not related
  to each other

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Optical Activity

• A substance is considered to be optically active
  when it can rotate plane-polarized light
• Plane-polarized light is obtained when ordinary
  light, which consists of radiation oscillating in
  an infinite number of planes, passes through a
  device called a polarizer, in which light that
  oscillates through a single plane passes through

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Optical Activity (cont.)

• Optically active molecules can rotate
  plane-polarized light to the right
  (dextrorotatory) or to the left (levorotatory)
• Rotation to the right is given a () sign,
  whereas rotation to the left is given a (-) sign

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Optical Activity (cont.)

• Optical activity is measured by a device called a
  polarimeter
• A polarimeter consists of the following 1) a
  light source, usually a sodium lamp 2) a sample
  cell 3) a polarizer, in order to convert ordinary
  light into polarized light and 4) an analyzer

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Specific Rotation

• Optical activity can be measured quantitatively
  by using a parameter called specific rotation
  (aD)
• Specific rotation is measured based on the
  relationship of the cell pathlength (measured in
  dm), concentration (g/mL) and the optical
  rotation of the compound

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Racemic Mixtures

• A racemic mixture ( or a racemate) is a mixture
  that contains a equal amount of two enantiomers.
  Given the symbol ()
• A racemic mixture is considered to be optically
  inactive because the specific rotation of the two
  enantiomers will cancel out each other

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Optical purity

• The ratio of its rotation to the rotation of a
  pure enantiomer

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Enantiomeric excess

• The excess of one enantiomer in a mixture of
  enantiomers expressed as a percentage of the
  mixture
• E.e. excess of one over the other/mixture x 100

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Racemic Mixtures Resolution (cont.)

• The diastereomers can be separated by ordinary
  physical methods (why?), and then each can be
  converted to the enantiomers that originated from
  the racemic mixture

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Fischer projections

• Fischer projections are the standard means of
  depicting projections at chiral centers
• Fischer projections by sets of horizontal and
  vertical lines. Horizontal lines indicate that
  the groups are pointed towards the plane, whereas
  vertical lines indicate groups that are pointed
  away from the plane

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Fischer projections (cont.)

• In testing to determine whether two Fischer
  projections are identical or enantiomers, either
  one of the two motions are allowed
• Rotating the entire molecule by 180o

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Fischer projections (cont.)

• A Fischer projection can have one group held
  steady, while rotating the other three clockwise
  or counterclockwise
• After performing either one of these motions with
  the molecule, the final projection is compared
  with the previous projection in order to
  determine whether the projection formulas are
  identical or enantiomers

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Assigning R,S Configurations to Fischer
projections

• The rules for assigning R and S configurations
  for Fischer projections are similar to those of
  previous stereoisomers
• Assign priorities to each functional group
  attached to the chiral carbon
• Orient the molecule such that the lowest priority
  group is in the rear of the molecule. This will
  place that group on top

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Assigning R,S conventions to Fischer projections
(cont.)

• Assign the R or S configuration based on the
  direction of rotation of the remaining three
  groups

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Enantiomers Diastereomers

• Recall that enantiomers are optically active
  compounds which are superimposable mirror images
  of each other
• Enantiomers have the same identical physical
  properties and chemical reactivities. They
  differ only in the direction they rotate
  plane-polarized light and configuration on the
  chiral carbon

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Enantiomers Diastereomers (cont.)

• Keep in mind that the mirror image of a clockwise
  rotation is a counterclockwise rotation (Hint
  try twirling your finger in a clockwise direction
  in the mirror, and see which direction the mirror
  image moves. Also, the mirror image of a R
  configuration on that chiral carbon is a S
  configuration

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Diasteromers

• Diastereomers are optical isomers which are not
  mirror images of each other
• Chiral carbons have opposite configurations at
  some chiral carbons, but have same configuration
  at some others. Enantiomers, on the other hand
  have opposite configuration at all chiral carbons

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Diastereomers

• Diastereomers have different physical properties
  and similar (but not identical) chemical
  properties.
• In terms of specific rotation, they can same or
  different signs or different magnitudes, whereas
  enantiomers have the same magnitude, but
  different signs

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Molecules with multiple chiral centers

• A molecule with n chiral centers can have a
  maximum of 2n stereoisomers. For instance, a
  molecule that has 3 chiral centers can have a
  maximum of 23 or 8 possible stereoisomers

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Meso Compounds

• Meso compounds are stereoisomers in which a plane
  of symmetry exists within the molecule itself,
  even though the molecule can have one or more
  chiral carbons.
• They are considered to be achiral and optically
  inactive.

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Resolution

• Since enantiomers have identical chemical and
  physical properties, one cannot separate a
  racemic mixture by ordinary physical methods but
  instead, must be done by resolution
• Resolution is based on the concept of reacting an
  optically active (e.g. chiral) reagent with the
  racemic mixture.

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Resolution (cont.)

• A racemic mixture of chiral acids can be
  separated by using an optically pure chiral base,
  whereas a racemic mixture of chiral bases can be
  separated by using an optically pure chiral acid.
  In both cases, a mixture of diastereomeric salts
  is formed, which can be separated physically and
  converted to the original enantiomer

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Resolution (cont.)

• Optically active compounds can be obtained from
  natural sources, since most living organisms can
  usually produce one enantiomer in a pair.

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Chirality and Nature

• Enantiomers can have different biological
  properties. In many cases, one enantiomer
  usually possess biological activity, whereas the
  other does not
• In organisms, enzymes can distinguish two
  enantiomers from each other