Organic Chemistry

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Organic Chemistry
William H. Brown Christopher S. Foote
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Chirality

• Chapter 3

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Isomers

• Isomers different compounds with the same
  molecular formula
• Constitutional isomers isomers with a different
  connectivity
• Stereoisomers isomers with the same molecular
  formula and connectivity but a different
  orientation of their atoms in space

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Isomers
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Chirality

• Mirror image the reflection of an object in a
  mirror
• Chiral an object that is not superposable on its
  mirror image an object that shows handedness
• Achiral an object that lacks chirality an
  object that has no handedness
• an achiral object has at least one element of
  symmetry

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Elements of Symmetry

• Plane of symmetry an imaginary plane passing
  through an object dividing it so that one half is
  the mirror image of the other half

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Elements of Symmetry

• Plane of symmetry (contd.)

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Elements of Symmetry

• Center of symmetry a point so situated that
  identical components of the object are located on
  opposite sides and equidistant from the point
  along any axis passing through it

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Stereocenter

• The most common (but not the only) cause of
  chirality in organic molecules is a tetrahedral
  atom, most commonly carbon, bonded to four
  different groups
• A carbon with four different groups bonded to it
  is called a stereocenter or, alternatively, a
  stereogenic center

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Enantiomers

• Enantiomers stereoisomers that are
  nonsuperposable mirror images refers to the
  relationship between pairs of objects
• On the three following screens are examples
  chiral molecules. Each has one stereocenter and
  can exist as a pair of enantiomers.

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Enantiomers

• Lactic acid

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Enantiomers

• 2-Chlorobutane

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Enantiomers

• 3-Chlorocyclohexene

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Enantiomers

• A nitrogen stereocenter

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R,S Convention

• Priority rules
• 1. Each atom bonded to the stereocenter is
  assigned a priority based on atomic number the
  higher the atomic number, the higher the priority
• 2. If priority cannot be assigned per the atoms
  bonded to the stereocenter, look to the next set
  of atoms priority is assigned at the first point
  of difference

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R,S Convention

• 3. Atoms participating in a double or triple bond
  are considered to be bonded to an equivalent
  number of similar atoms by single bonds

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Naming Enantiomers

• 1. Locate the stereocenter, identify its four
  substituents, and assign priority from 1
  (highest) to 4 (lowest) to each substituent
• 2. Orient the molecule so that the group of
  lowest priority (4) is directed away from you
• 3. Read the three groups projecting toward you in
  order from highest (1) to lowest priority (3)
• 4. If the groups are read clockwise, the
  configuration is R if they are read
  counterclockwise, the configuration is S
• (S)-2-Chlorobutane

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R,S Configuration

• (R)-3-Chlorocyclohexene
• (R)-Mevalonic acid

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Enantiomers Diastereomers

• For a molecule with 1 stereocenter, 21 2
  stereoisomers are possible
• For a molecule with 2 stereocenters, a maximum of
  22 4 stereoisomers are possible
• For a molecule with n stereocenters, a maximum of
  2n stereoisomers are possible

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Enantiomers Diastereomers

• 2,3,4-trihydroxybutanal
• two stereocenters 22 4 stereoisomers exist

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Enantiomers Diastereomers

• 2,3-dihydroxybutanedioic acid (tartaric acid)
• two stereocenters 2n 4, but for this molecule,
  only three stereoisomers exist
• Meso compound an achiral compound possessing two
  or more stereocenters

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Enantiomers Diastereomers

• 2-methylcyclopentanol

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Enantiomers Diastereomers

• 1,2-cyclopentanediol

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Enantiomers Diastereomers

• cis-3-methylcyclohexanol

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Enantiomers Diastereomers

• trans-3-methylcyclohexanol

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Properties of Stereoisomers

• Enantiomers have identical physical and chemical
  properties in achiral environments
• Diastereomers are different compounds and have
  different physical and chemical properties
• Meso-tartaric acid, for example, has different
  physical and chemical properties from its
  enantiomers (see Table 3.1).

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Plane-Polarized Light

• Ordinary light light vibrating in all planes
  perpendicular to its direction of propagation
• Plane-polarized light light vibrating only in
  parallel planes
• plane polarized light is the vector sum of left
  and right circularly polarized light these two
  forms of light are enantiomers
• because of their handedness, each component of
  circularly polarized light interacts in an
  opposite way with a chiral molecule.

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Plane-Polarized Light
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Plane-Polarized Light

• because of its handedness, circularly polarized
  light reacts one way with an R stereocenter, and
  in an opposite with its enantiomer
• the net effect of the interaction of plane
  polarized light with a chiral compound is that
  the plane of polarization is rotated
• Polarimeter a device for measuring the extent of
  rotation of plane polarized light

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Optical Activity

• Observed rotation the number of degrees, ?,
  through which a compound rotates the plane of
  polarized light
• Dextrorotatory () refers to a compound that
  rotates the plane of polarized light to the right
• Levorotatory (-) refers to a compound that
  rotates of the plane of polarized light to the
  left

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Optical Activity

• Specific rotation observed rotation of the plane
  of polarized light when a sample is placed in a
  tube 1.0 dm in length and at a concentration of
  1g/mL

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Optical Activity

• For a pair of enantiomers, the value of the
  specific rotation of each is the same, but
  opposite in sign

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Enantiomeric Excess

• When dealing with a mixture of enantiomers, it is
  essential to describe the composition of the
  mixture and the degree to which one enantiomer is
  in excess
• The most common designation is enantiomeric
  excess (ee)

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Enantiomeric Excess

• Example a commercial synthesis of naproxen,
  a nonsteroidal antiinflammatory drug (NSAID),
  gives this enantiomer in 97 ee. Assign an R or S
  configuration to its stereocenter, and calculate
  the R and S enantiomers in the mixture.

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Resolution

• Racemic mixture an equimolar mixture of two
  enantiomers
• because a racemic mixture contains equal numbers
  of dextrorotatory and levorotatory molecules, its
  specific activity is zero.
• Resolution the separation of a racemic mixture
  into its enantiomers

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Resolution

• One means of resolution is to convert the pair of
  enantiomers into two diastereomers
• diastereomers are different compounds and have
  different physical properties
• A common reaction for chemical resolution is salt
  formation
• after separation of the diastereomers, the
  enantiomerically pure acids are recovered

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Resolution

• Examples of enantiomerically pure bases

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Resolution

• Enzymes as resolving agents

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Chirality in the Biological World

• Except for inorganic salts and a few
  low-molecular-weight organic substances, the
  molecules of living systems are chiral
• Although these molecules can exist as a number of
  stereoisomers, generally only one is produced and
  used in a given biological system
• Its a chiral world!

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Chirality in the Biological World

• Consider chymotrypsin, a protein-digesting enzyme
  in the digestive system of animals
• chymotrypsin contains 251 stereocenters
• the maximum number of stereoisomers possible is
  2251
• there are only 238 stars in our galaxy!

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Chirality in the Biological World

• Enzymes are like hands in a handshake
• the substrate fits into a binding site on the
  enzyme surface
• a left-handed molecule will only fit into a
  left-handed binding site and
• a right-handed molecule will only fit into a
  right-handed binding site
• enantiomers have different physiological
  properties because of their handedness of their
  interactions with other chiral molecules in
  living systems

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Chirality in the Biological World
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Prob 3.15

• Draw mirror images for each molecule.

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Prob 3.16

• Which are identical with (a) and which are
  mirror images of (a)?

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Prob 3.17

• Mark all stereocenters in each molecule.

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Prob 3.20

• Assign an R or S configuration to the
  stereocenter in each enantiomer.

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Prob 3.21

• Assign an R or S configuration to this
  enantiomer of 2-butanol. Also draw a Newman
  production viewed along the bond between carbons
  2 and 3.

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Prob 3.22

• Assign an R or S configuration to each
  stereocenter in this enantiomer of ephedrine.

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Prob 3.23

• Assign an R or S configuration to this
  enantiomer of carbon-14 labeled citric acid.

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Prob 3.24

• Draw all stereoisomers possible for this
  compound. Label which are meso and which are
  pairs of enantiomers.

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Prob 3.25

• Mark are stereocenters in each molecule. How
  many stereoisomers are possible for each molecule?

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Prob 3.26

• Label the eight stereocenters in cholesterol.

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Prob 3.27

• Label the four stereocenters in amoxicillin.

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Prob 3.29

• Are the formulas in each set identical,
  enantiomers, or diastereomers?

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Prob 3.30

• Which are meso compounds?

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Prob 3.31

• Oxidation of this bicyclic alkene gives a
  dicarboxylic acid. Is the product of this
  oxidation one enantiomer, a racemic mixture, or a
  meso compound?

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Prob 3.35

• Verify that although, this molecule has no
  stereocenter, it is chiral.

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Prob 3.36

• Verify that, although this substituted allene
  has no stereocenter, it is chiral.

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Chirality
End of Chapter 3