Organic Chemistry

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Organic Chemistry

• Dr. Ibrahim Ahmed Ibrahim

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Stereoisomerism and Chirality
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Chirality

• Chiral from the Greek, cheir, hand
• Achiral an object that lacks chirality one that
  lacks handedness
• an achiral object has at least one element of
  symmetry

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Chirality Centers

• A point in a molecule where four different groups
  (or atoms) are attached to carbon is called a
  chirality center
• A chiral molecule usually has at least one
  chirality center

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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 connectivity
  but a different orientation of their atoms in
  space

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A Brief Review of Isomerism

• The flowchart summarizes the types of isomers we
  have seen

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• The term "isomer" (iso from the Greek meaning
  same and meros meaning part)
• Isomerism consists of three types
• a) Structural isomerism
• b) Stereoisomerism
• 1- geometrical isomerism
• 2- optical isomerism
• C) Conformations

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• Structural isomerism
• 1- Chain isomerism
• This type of isomerism compounds differ in
  arrangement of carbon
• C4H10, C4H8

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Constitutional Isomers

• Different order of connections gives different
  carbon backbone and/or different functional groups

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• 2-Position isomerism
• This type of isomerism is exhibited in compounds
  having the carbon skeletion but differ in the
  position of the functional group

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• B)Stereoisomerism
• Stereoisomerism is exhibited by isomers having
  the same structures but differ in their
  configuration
• i- Geometrical isomerism

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Alkenes
cis-but-2-ene
trans-but-2-ene
Diastereomers (does not deviate the polarized
light)
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E/Z Convention for Alkenes

• E Entgegen (opposite)
• Z Zusammen (with)
• Identify the highest atomic number

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1
1
1
I gt Br
Br gt C
1
2
2
2
E
Z
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Chiral Center

• 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 chiral center
• Enantiomers stereoisomers that are mirror images
  for each other
• refers to the relationship between pairs of
  objects

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Examples of Enantiomers

• Molecules that have one carbon with 4 different
  substituents have a nonsuperimposable mirror
  image enantiomer
• Build molecular models to see this

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Sect 5.2 Enantiomers
Four different atoms are attached to a chiral
carbon atom. Mirror images are
non-superimposable.
rotate
this molecule is chiral
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An achiral molecule
A carbon atom with three identical groups is
achiral! There is a symmetry plane in the plane
of the paper.
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plane of symmetry
side view
edge view
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Another achiral molecule
This molecule has a plane of symmetry in the
plane of the paper.
These two structures are superimposable!
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identification of stereocenters
Look for carbon atoms with four different
groups!


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Enantiomers

• The enantiomers of lactic acid
• drawn in two different representations

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Enantiomers

• 2-Chlorobutane

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Enantiomers

• 3-Chlorocyclohexene

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Enantiomers

• A nitrogen chiral center

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Enantiomers Diastereomers

• For a molecule with 1 chiral center, 21 2
  stereoisomers are possible
• For a molecule with 2 chiral centers, a maximum
  of 22 4 stereoisomers are possible
• For a molecule with n chiral centers, a maximum
  of 2n stereoisomers are possible

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Sect. 5.4 Properties of Enantiomers

• Enantiomers interact differently with polarized
  light.
• Enantiomers have equal magnitude, but opposite
  signs of rotation
• Most other properties are identical.
• Odor may be different!!

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Enantiomers Diastereomers

• 2,3,4-Trihydroxybutanal
• two chiral centers
• 22 4 stereoisomers exist two pairs of
  enantiomers
• Diastereomers
• stereoisomers that are not mirror images
• refers to the relationship among two or more
  objects

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Enantiomers Diastereomers

• 2,3-Dihydroxybutanedioic acid (tartaric acid)
• two chiral centers 2n 4, but only three
  stereoisomers exist
• Meso compound an achiral compound possessing two
  or more chiral centers that also has chiral
  isomers

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Enantiomers Diastereomers

• 2-Methylcyclopentanol

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Enantiomers Diastereomers

• 1,2-Cyclopentanediol

H
H
H
H
diastereomers
H
H
H
H
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Enantiomers Diastereomers

• cis-3-Methylcyclohexanol

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Enantiomers Diastereomers

• trans-3-Methylcyclohexanol

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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

• Has wave properties reflecting a periodic
  increase and decrease in amplitude of wave

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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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Rotation of plane-polarized light
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Plane-Polarized Light

• Polarimeter a device for measuring the extent of
  rotation of plane-polarized light

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Specific rotation

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

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Specific Rotation and Molecules

• Characteristic property of a compound that is
  optically active the compound must be chiral
• The specific rotation of the enantiomer is equal
  in magnitude but opposite in sign

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Racemic mixture

• A mixture containing equal quantities of
  enantiomers is called a racemic mixture
• a racemic mixture is optically inactive (? 0)
• A sample that is optically inactive can
  beeither an achiral substance or a
  racemicmixture

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Specific rotation

• () and (-) notation
• Dextrorotatory ()
• Levorotatory (-)
• (?) racemic mixture of enantiomers

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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
• specific rotation observed rotation when a pure
  sample is placed in a tube 1.0 dm in length and
  concentration in g/mL (density) for a solution,
  concentration is expressed in g/ 100 mL

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ENANTIOMERS HAVE EQUAL VALUES BUT OPPOSITE SIGNS
OF ROTATIONS
W
W
Enantiomers
C
C
Y
X
X
Y
Z
Z
()-numbero
(-)-numbero
dextrorotatory
levorotatory
The numbers are the same, but have opposite
signs. All other physical properties are
IDENTICAL.
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Physical properties of enantiomers

• Same melting point, boiling point, density,
  etc
• Different properties that depend on shape of
  molecule (biological-physiological properties)
  can be different

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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 rotation 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

• racemic acids can be resolved using commercially
  available chiral bases such as 1-phenylethanamine
• racemic bases can be resolved using chiral acids
  such as

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Enantiomers or Diastereomers?

• Threonine

aD25 28
aD25 -28
L-threonine
D-threonine
aD25 9
aD25 -9
L-allo-threonine
D-allo-threonine
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D/L Convention

• Amino acids
• Contain an amino group and a carboxylic acid
  group a side chain
• . Functional group is left L-amino acid.

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Examples

• L-Valine D-Valine
• D-Lactic Acid

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Glyceraldehyde(an aldotriose)
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There are four natural pentose sugars. They have
the D configuration.
OH points to right! D
OH points to right! D
OH points to right D
OH points to right D
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The Aldotetroses
Notice that the D enantiomers are (-)!
Notice that the L Enantiomers are ()!
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Chirality in the Biological World

• Consider chymotrypsin, a protein-digesting enzyme
  in the digestive system of animals
• chymotrypsin contains 251 chiral centers
• the maximum number of stereoisomers possible is
  2251

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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 the handedness of their
  interactions with other chiral molecules in
  living systems

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Chirality in the Biological World

• a schematic diagram of an enzyme surface capable
  of binding with (R)-glyceraldehyde but not with
  (S)-glyceraldehyde

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How Many Stereoisomers Are Possible?
maximum number of stereoisomers 2n, where n
number of stereocenters
For the previous example two stereocenters 4
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Determining the number of possible
stereoisomers


22 4 stereoisomers



23 8 stereoisomers
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Isomers - same molecular formula - different
compounds
constitutional isomers - different connectivity
stereoisomers - same connectivity - different
orientation in space (recall cis/trans)
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Chiral Center

• common source of chirality - tetrahedral (sp3)
  carbon (atom) - bonded to 4 different groups

chiral center - carbon (atom) with 4 different
groups
Enantiomers stereoisomers nonsuperposable
mirror images
All chiral centers are stereocenters
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Diastereomers

• Molecules with more than one chirality center
  have mirror image stereoisomers that are
  enantiomers
• In addition they can have stereoisomeric forms
  that are not mirror images, called diastereomers

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Meso Compounds

• Tartaric acid has two chirality centers and two
  diastereomeric forms
• One form is chiral and the other is achiral, but
  both have two chirality centers
• An achiral compound with chirality centers is
  called a meso compound it has a plane of
  symmetry
• The two structures on the right in the figure are
  identical so the compound (2R, 3S) is achiral

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Chiral Control IssuesWide Variety of Drug Types
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20
10
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Approximate Proportion of the New Molecular
Entities approved in 1998/99 (http//www.fda.gov/
cder/rdmt/)
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Chiral drugs

• Ibuprofen is chiral, but normally sold asa
  racemic mixture. The S enantiomer is the one
  responsible for its analgesic and
  antiinflammatory properties.

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Stereoisomers

• Same connections, different spatial arrangement
  of atoms
• Enantiomers (nonsuperimposable mirror images)
• Diastereomers (all other stereoisomers)
• Includes cis, trans and configurational