Module - III
Stereochemistry and Organic reactions: Representations of
3 dimensional structures, Structural isomers and Stereoisomers,
Configurations and Symmetry, Chirality, Enantiomers,
Diastereomers, Optical activity, Absolute configurations,
Conformational analysis,
Introduction to reactions involving Substitution, Addition,
Elimination, Oxidation, Reduction, Cyclization, Ring openings,
Synthesis of a commonly used drug molecule.
Isomerism
Isomerism is the phenomenon in which more than one
compounds have the same chemical formula but different
chemical structures.
Chain Isomerism
1. It is also known as skeletal isomerism.
2. The components of these isomers display differently branched
structures.
3. Commonly, chain isomers differ in the branching of carbon
Position Isomerism
1. The positions of the functional groups or substituent atoms are
different in position isomers.
2. Typically, this isomerism involves the attachment of the functional
groups to different carbon atoms in the carbon chain.
formula C3H7Cl
Cl
Cl
1-chlorobutane
2-chlorobutane
Functional group isomerism
In this variety of structural isomerism, the isomers contain
different functional groups - that is, they belong to different families of
compounds
Metamerism
This type of isomerism arises due to the presence of different alkyl
chains on each side of the functional group.
It is a rare type of isomerism and is generally limited to molecules
that contain a divalent atom (such as sulphur or oxygen), surrounded by
alkyl groups.
Example: C4H10O can be represented as ethoxyethane (C2H5OC2H5) and
methoxy-propane (CH3OC3H7).
Tautomerism
A tautomer of a compound refers to the isomer of the
compound which only differs in the position of protons and electrons.
Typically, the tautomers of a compound exist together in
equilibrium and easily interchange.
It occurs via an intramolecular proton transfer.
An important example of this phenomenon is Keto-enol
tautomerism.
Ring-Chain Isomerism
In ring-chain isomerism, one of the isomers has an open-chain
structure whereas the other has a ring structure.
They generally contain a different number of pi bonds.
A great example of this type of isomerism can be observed in
C3H6.
Propene and cyclopropane are the resulting isomers.
Stereoisomerism
This type of isomerism arises in compounds having the same
chemical formula but different orientations of the atoms belonging to
the molecule in three-dimensional space.
The compounds that exhibit stereoisomerism are often
referred to as stereoisomers
Enantiomers
Enantiomers, also known as optical
isomers, are two stereoisomers that are related
to each other by a reflection: they are mirror
images of each other that are non-
superimposable.
(a) Bromochlorofluoromethane is a chiral molecule whose
stereocenter is designated with an asterisk. Rotation of its mirror
image does not generate the original structure. To superimpose the
mirror images, bonds must be broken and reformed. (b) In contrast,
dichlorofluoromethane and its mirror image can be rotated so they
are superimposable.
Diastereomers are stereoisomers not related through a reflection
operation.
They are not mirror images of each other. These
include meso compounds, cis–trans isomers, E-Z isomers, and non-
enantiomeric optical isomers.
D-Threose D-erythrose
Stereocenters are labeled R or S
The method of unambiguously assigning the handedness of
molecules was originated by three chemists: R.S. Cahn, C. Ingold, and V.
Prelog and, as such, is also often called the Cahn-Ingold-Prelog rules.
In addition to the Cahn-Ingold system, there are two ways of
experimentally determining the absolute configuration of an enantiomer:
X-ray diffraction analysis. Note that there is no correlation between the
sign of rotation and the structure of a particular enantiomer.
Chemical correlation with a molecule whose structure has already been
determined via X-ray diffraction.
Stereocenters are labeled R or S
The "right hand" and "left hand" nomenclature is used to name the
enantiomers of a chiral compound.
The stereocenters are labeled as R or S.
"Sinister" → Latin= "left" "Rectus" → Latin= "right"
A curved arrow is drawn from the highest priority (1) substituent to the
lowest priority (4) substituent. If the arrow points in a counterclockwise
direction, the configuration at stereocenter is considered ”S”. If,
however, the arrow points clockwise, then the stereocenter is labeled
1. S: I > Br > F > H.
The lowest priority
substituent. H, is
already going
towards the back
2. R: Br > Cl > CH3 > H. You
have to switch the H and Br in
order to place the H, the lowest
priority, in the back. Then,
going from Br to Cl, CH3 is
turning to the right, giving you
a R.
3. Neither R or S: This molecule is achiral.
4. R: OH > CN > CH2NH2 > H. The H, the lowest priority, has to be
switched to the back.
5. S: −COOH>−CH2OH> C≡CH>HH.
Then,going from −COOH to −CH2OH to −C≡CH−you are turning
left, giving you a S configuration.
Conformation of n-Butane
Click the below link for 3D view of
conformations of n- butane
[Link]
n-Butane is an alkane with the presence of C-C bonds.
Normally, when we rotate the molecule of butane at the axis of the
C-C bond, it shows different conformation isomerism. Generally,
Butane has four conformation isomers which are fully eclipsed,
gauche, eclipsed, and anti butane conformational isomers.
Ranking of Conformation Isomers
The ranking of the conformational isomers is given below taking into
account the energy levels from lowest to highest. It is given as;
1. Anti (more stable)
2. gauche
3. eclipsed
4. fully eclipsed