Stereochemistry

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Stereochemistry
Stereochemistry
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1. Flying-Wedge or Wedge-Dash projection The
Flying-Wedge projection is the most common
three-dimensional representation of a three
dimensional molecule on a two dimensional surface
(paper). This kind of representation is usually
done for molecules containing chiral centre. In
this representation, the ordinary lines represent
bonds in the plane of the paper. A solid Wedge (
) represents a bond above the plane of
the paper and a dashed wedge ( ) or a
broken line ( ) represents a bond below
the plane of the paper.

Methane
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The Flying-Wedge projection formula of (R)-
Lactic acid , for example, can be shown as
follows..

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• 2. FISCHER PROJECTION FORMULAE
• The carbon chain is projected vertically, the
  horizontal bonds attached to a carbon are
  considered to be above the plane of the paper and
  towards the viewer and the vertical bonds are
  considered to be below the plane of the paper and
  at the back of viewer.
• In Fischer Formula, if two like groups are on the
  same side, the molecule is called Erythro and
  if two like groups are on opposite side it is
  called threo .

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• 3. SAWHORSE FORMULAE
• In this representation, the molecule is viewed
  slightly from above and form the right and then
  projected on the paper. The bond between the two
  carbon atoms is drawn diagonally and of a
  relatively greater length for the sake of
  clarity. The lower left hand carbon is taken as
  the front carbon and the upper right hand carbon
  as the back carbon .
• All parallel bonds in sawhorse formula are
  Eclipsed and all anti parallel bonds are opposite
  or trans/anti to each other. The sawhorse
  presentation of Eclipsed and staggered
  conformations of Ethane are as follow.

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• 4. NEWMAN PROJETION FORMULAE
• Newman devised a very simple method of projecting
  three dimensional formula on paper which are
  known as Newman projections.
• In these Formulae the molecule is viewed from the
  front. The carbon atom nearer to the eye is
  represented by a point and the three atoms or
  groups are shown attached to it by three lines at
  an angle of 1200 to each other.
• In Newmans formula all parallel bonds are
  Eclipsed and all anti- parallel (or) opposite
  bonds are

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• Newman projections for Eclipsed and staggered
  conformation of Ethane are

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I S O M E R I S M
Isomers are molecules that have the same
molecular formula, but have a different
arrangement of the atoms in space.
Stereoisomers- In stereoisomerism, the atoms
making up the isomers are joined up in the same
order, but still manage to have a different
spatial arrangement.
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Conformational isomerism
Conformations of Acyclic Alkanes
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• Different conformations differ in their energy
  content. Energy is maximum when two bond pairs
  are closest to each other. This is the eclipsed
  conformation, the CH bonds on one carbon are
  directly aligned with the CH bonds on the
  adjacent carbon. This is the most unstable form.
• In the staggered conformation, the CH bonds on
  one carbon bisect the HCH bond angle on the
  adjacent carbon. The energies are minimum as the
  bond pairs are as far as possible. This is most
  stable form.

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• Rotating the atoms on one carbon by 60 converts
  an eclipsed conformation into a staggered
  conformation, and vice versa.
• The angle that separates a bond on one atom from
  a bond on an adjacent atom is called a dihedral
  angle. For ethane in the staggered conformation,
  the dihedral angle for the CH bonds is 60. For
  eclipsed ethane, it is 0.

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Cnformational Analysis of Ethane

• Conformations are different spatial arrangements
  of a molecule that are generated by rotation
  about single bonds.

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Ethanes Conformations

• The most stable conformation of ethane has all
  six CH bonds away from each other (staggered).
• The least stable conformation has all six CH
  bonds as close as possible (eclipsed) in a Newman
  projection.

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Ethanes Conformations

• The barrier to rotation between conformations is
  small (12 kJ/mol 2.9 kcal/mol)
• The eclipsed conformers are 12 kJ/mol higher in
  energy than the staggered conformers energy due
  to torsional strain

Dihedral angle
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Ethane

• eclipsed conformation

• staggered conformation

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Conformational Analysis of Butane
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Butanes Conformations

• anti conformation is the most stable conformation
  of butane .It has two methyl groups 180 away
  from each other.

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Butanes Conformations

• Rotation around the C2C3 gives eclipsed
  conformation, the methyl groups are too close.
• 16kJ/mol is due to steric and torsional strain.
  

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Butanes Conformations

• gauche conformation is the staggered conformation
  with methyl groups 60 apart.
• Although it has no eclipsing interactions, it is
  3.8 kJ/mol higher in energy than the anti
  conformation.
• This is due to steric strain.

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Butanes Conformations
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Chirality
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 all
chiral centers are stereocenters, but not all
stereocenters are chiral centers Enantiomers
stereoisomers that are nonsuperposable mirror
images refers to the relationship between pairs
of objects
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Optical Rotation and Polarimetry
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Optical Rotation and Polarimetry
The amount (in degrees) that a chiral material
will rotate light is called the optical rotation.
Different chiral molecules will have optical
rotations that vary in direction and size of the
optical rotation. Enantiomers will always have
equal optical rotations but in opposite
directions.
The optical purity of a substance can be measured
by comparing the optical rotation of the sample
to the known optical rotation of a single
entantiomer of that compound. Optical purity is
usually reported in percent entantiomeric excess
(ee).
Enantiomeric excess is the of the sample that
is non-racemic. For example, 80 ee means that
there is 90 of one enantiomer and 10 of the
other.
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• RACEMISATION
• By the action of heat
• By treatment with chemical reagents
• Autoracemisation

• RESOLUTION OF A RACEMIC MIXTURE
• The separation of a racemic mixture into its two
  enantiomers is called resolution.
• Mechanical method Physical Difference -Pasteur
  separated the crystals of sodium ammonium
  tartarate Na(NH4) C4H4O62H2O (Racemate). Since
  this method brings experimental difficulties and
  has only limited application, it is only of
  historical importance now.
• Biochemical method Penicilium glaucum (a mould)
  when grown in a dilute solution of a racemate, it
  attacks the dextro from leaving behind the laevo
  form. Thus, the laevo form remains practically
  unaffected. Although, it is a slow method yet it
  is of wide application. Biochemcal method of
  separation has some disadvantages.
• i) One form is always destroyed
• ii) As dilute solutions re used, the amount
  of the second isomer left behind is very
• small.
• iii) It is difficult to select a
  micro-organism which attacks only one of the
  enantiomers

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• Chemical method (Resolution by salt formation)-
  separation of racemic mixture of lactic acid. The
  racemic mixture of lactic acid is treated with
  1-brucine ( a base) when salts, called
  diastereomers are obtained.
• dl lactic acid I brucine ?
  I-brucine-d-lactateI-brucine I-lactate.
  
• The two lactates (diastereomers) are then
  separated by fractional crystallisation and then
  each is separately treated with HCI to get the
  two enantiomers of lactic acid.
  
  
• I-brucine-d-lactateHCI? d-lactic acid
  I-brucine. HCI
  I-brucine-I-lactateHCI
  ? I-lactic acid I-brucine. HCI

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• 4. Kinetic method Diffrence in rate of
  reaction - resolution of racemic mandelic acid
  I-menthol (an alcohol) reacts faster with
  d-mandelic acid than with I-mandelic acid to form
  ester. Clearly, when, dI-mandelic acid (a racemic
  mixture) is treated with limited quantity of
  I-menthol, the product formed is rich in d-ester
  then I-ester.
• Selective adsorption- One of the enantiomers is
  selectively adsorbed on the surface of the
  adsorbent. The solution collected at the bottom
  of the adsorbent column is richer in the other
  enantiomer. This results in the separation of
  the racemic mixture.

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Examples of Enantiomers

• Molecules that have one carbon with 4 different
  substituents have a non-superimposable mirror
  image
• Enantiomers non-superimposable mirror image
  stereoisomers
• Build molecular models to see this

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Types of Stereoisomers

• Stereo isomers contains same molecular formula,
  same bonding sequence, different spatial
• orientation.
• Two types of stereoisomers
• Enantiomers (Mirror image)
• two compounds that are nonsuperimposable mirror
  images of each other
• Diastereomers (Non-Mirror Image)
• Two stereoisomers that are not mirror images of
  each other
• Geometric isomers (cis-trans isomers) are one
  type of diastereomer.

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Geometric (cis / trans) isomerism
In one, the two chlorine atoms are locked on
opposite sides of the double bond. This is known
as the trans isomer. (trans from latin meaning
"across" - as in transatlantic). In the other,
the two chlorine atoms are locked on the same
side of the double bond. This is know as the cis
isomer. (cis from latin meaning "on this
side")
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E-Z NOTATION The simple convention of denoting
the geometrical isomers by cis/trans descriptors
is not sufficient when there are more than two
different substituents on a double bond. To
differentiate the stereochemistry in them, a new
system of nomenclature known as the E-Z notation
method is to be adopted. According to this
method, if the groups with higher priorities are
present on the opposite sides of the double bond,
that isomer is denoted by E. Where E Entgegen 
( the German word for 'opposite') However, if the
groups with higher priorities are on the same
side of the double bond, that isomer is denoted
by Z. Where Z Zusammen (the German word for
'together') The letters E and Z are represented
within parentheses and are separated from the
rest of the name with a hyphen.  
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E,Z Configuration

• uses priority rules
• higher priority groups - same side, Z

E
Z
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•  Step by step procedure to determine the E-Z
  configuration
• The following procedure is to be adopted to
  denote the geometrical isomers by E Z
  descriptors. 
• First determine the higher priority group on each
  end of the double bond. 
• If the higher priority groups are on the opposite
  sides of double bond, the isomer is denoted by
  the descriptor, E. 
• Otherwise if they are on the same side of double
  bond, the Z descriptor must be used.

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• CahnIngoldPrelog priority rules
• Assignment of priorities
• R/S and E/Z descriptors are assigned by using a
  system for ranking priority of the groups
  attached to each stereocenter.
• Compare the atomic number (Z) of the atoms
  directly attached to the stereocenter the group
  having the atom of higher atomic number receives
  higher priority.
• 2. If there is a tie, we must consider the atoms
  at distance 2 from the stereocenteras a list is
  made for each group of the atoms bonded to the
  one directly attached to the stereocenter. Each
  list is arranged in order of decreasing atomic
  number. Then the lists are compared atom by atom
  at the earliest difference, the group containing
  the atom of higher atomic number receives higher
  priority.
• 3 A double or triple bond atom is considered as 2
  or 3 of each atom.

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