Stereochemistry
-- a subdiscipline of chemistry, which involves the study of the relative spatial
arrangement of atoms that form the structure of molecules and their manipulation.
Syllabus
Isomerism
Types of Isomerism
Structural Isomers
Structural Isomers
CHAIN ISOMERISM
Structural Isomers
What is Tautomerism?
Tautomerism is a phenomenon where a single chemical compound tends to exist in
two or more interconvertible structures that are different in terms of the relative
position of one atomic nucleus which is generally the hydrogen. The two structures
are called tautomers and these type of isomer compounds usually differ only in the
number of electrons and protons. They also exist in dynamic equilibrium.
Stereoisomers
➢ Thalidomide was first marketed in 1957
in West Germany, for anxiety, trouble
sleeping, "tension", and morning
sickness.
➢ Thalidomide is racemic; while R-
thalidomide is the bioactive form of the
molecule, the individual enantiomers can
racemize to each other due to the acidic
hydrogen at the chiral centre
In November 1961, thalidomide was taken
off the market due to massive pressure from
the press and public. Experts estimate that
the drug thalidomide led to the death of
approximately 2,000 children and serious
birth defects in more than 10,000 children,
about 5,000 of them in West Germany.
Stereoisomers
Enantiomers - Mirror images
Diastereomers
Diastereomers are stereoisomers that are not mirror images of each other and non-
superimposable. Diastereomers can have different physical properties and reactivity.
They have different melting points and boiling points and different densities. They
have two or more stereocenters.
Chiral Molecules, Optically Inactive – Racemic Mixture
Optical Activity
Optical Rotation
Optically Active
Meso-Compound – Optically Inactive
How can a compound be optically active without
chiral carbon?
Configuration
Sequence Rules -- Cahn, Ingold, Prelog
➢ The Cahn–Ingold–Prelog (CIP) sequence rules, named for organic chemists Robert
Sidney Cahn, Christopher Kelk Ingold, and Vladimir Prelog — alternatively termed
the CIP priority rules, system, or conventions — are a standard process used in
organic chemistry to completely and unequivocally name a stereoisomer of a
molecule.
➢ The purpose of the CIP system is to assign an R or S descriptor to each
stereocenter and an E or Z descriptor to each double bond so that the
configuration of the entire molecule can be specified uniquely by including the
descriptors in its systematic name.
Sequence Rules -- Cahn, Ingold, Prelog
Steps for naming
➢ The steps for naming molecules using the CIP system are often presented as:
▪ Identification of stereocenters and double bonds;
▪ Assignment of priorities to the groups attached to each stereocenter or double-
bonded atom
▪ Assignment of R/S and E/Z descriptors.
Sequence Rules -- Cahn, Ingold, Prelog
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. This procedure, often known as the sequence rules, is the
heart of the CIP system.
1. 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 stereocenter—as 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. If there is still a tie, each atom in each of the two lists is replaced with a sublist of the
other atoms bonded to it (at distance 3 from the stereocenter), the sublists are
arranged in decreasing order of atomic number, and the entire structure is again
compared atom by atom. This process is repeated recursively, each time with atoms one
bond farther from the stereocenter, until the tie is broken.
Assignment of priorities
Assign R/S configuration for each of the following molecules
S R
R
Achiral – R/S NA
3 1
2
S
Double bonds: E/Z notation
➢ For alkenes and similar double bonded molecules, the same prioritizing process is followed
for the substituents. In this case, it is the placing of the two highest priority substituents
with respect to the double bond which matters. If both high priority substituents are on
the same side of the double bond, i.e. in the cis configuration, then the stereoisomer is
assigned a Z (zusammen) . If by contrast they are in a trans configuration, then the
stereoisomer is assigned an E (entgegen). In this case the identifying letters are derived
from German for 'together' and 'opposite', respectively.
Fischer D and L Nomenclature
chiral
Relative Configuration
d l
l
• Due to free rotation along the central bond, two conformations are
possible – the staggered and eclipsed.
Rear
Carbon CO2H
H OH
Rotation by 180°
along C2-C3 bond HO H
HO
H HO
CO2H H
CO2H CO2H
Eclipsed Staggered
Sawhorse Projection
H Br
CH3
CH3
H Br
Br H
Br H
CH3 CH3
Eclipsed Fischer Projection
Sawhorse Projection
Conformational analysis: Conformations of
n-butane
Di
