STEREOCHEMISTRY

The detailed study of three dimensional structure of organic

compounds.
Isomerism: The compounds having same molecular formula but
differ from each other in physical and chemical properties are called
isomers and this phenomenon is called as Isomerism.
Constitutional/structural isomers have different IUPAC names, the same or
different functional groups, different physical properties and different
chemical properties.

Stereoisomers differ only in the way the atoms are oriented in space. They
have identical IUPAC names (except for a prefix like cis or trans). They always
have the same functional group(s).

A particular three-dimensional arrangement is called a configuration.

Stereoisomers differ in configuration.
Stereoisomers are isomers that differ in spatial arrangement of atoms, rather
than order of atomic connectivity.

Configurational Isomers: Two molecules with the same constitution but

different configuration (i.e. – same IUPAC name for constitution,
different IUPAC prefix for configuration).
Configurational isomers cannot be interconverted without breaking
bonds.
Optical isomers are two compounds which contain the same number and kinds
of atoms, and bonds (i.e., the connectivity between atoms is the same), and
different spatial arrangements of the atoms, but which have non-
superimposable mirror images. Each non-superimposable mirror image
structure is called an enantiomer.
Enantiomers contain chiral centers that are non-superimposable &
mirror images. ... Diastereomers contain chiral centers are non-
superimposable but are NOT mirror images
conformational isomerism is a form of stereoisomerism in which the isomers
can be interconverted just by rotations about formally single bonds .

OPTICAL ISOMERISM
The compounds which have same molecular and structural formula but differ
only in their action towards the plane polarized light or optical activity are
known as optical isomers and the phenomenon is known as optical isomers.
Specific Rotation : It is a number of degrees of rotation of plane polarized light
produced by one gram of the substance per ml and the length of the tube is
unity too.
In optical activity, Compounds that rotate the plane polarized light to the right
(clockwise) ae called as Dextrorotatory. d(+)

Compounds that rotate the plane polarized light to the left (anti clockwise) ae
called as Dextrorotatory. d(-)
Condition for Optical Activity

The geometrical structure of the molecule should not superimpose on its

mirror image ie it must exists in enantiomeric form.
Substances should be light sensitivity.
They should have chiral carbon
They should rotate the PPL.
Further more it should be devoid of the following elements of symmetry

A plane of symmetry
A center of symmetry
An alternating axis of symmetry
How much excess S enantiomer is
present in excess
40% optically active means- 40% is in excess S enantiomers, 60% racemic
mixture
S enatiomers= ½ (Racemic mixture) + Excess S enantiomers
= ½(60) + 40= 70S and 30R
Example: A solution was made by mixing 10ml of 0.1M solution of R
enantiomers nd 30ml of .1M solution of S enantiomers was found to have an
observed specific rotation +4.80 .What is the specific rotation of each of the
enantiomers.
R- one mole = 10mlx.1M = 1mmole
S : 30 x .1= 3 mmole
1R+1S =2 mmole of racemic mixture
Excess 2 mmole of S left
Optical purity = 2/4 = obs specific rotation /Sp rotation of Pure enantiomers
0.50= +4.8/x
X = +9.6
S = +9.6 and R = -9.6
Types of Optical isomers:
1. Enantiomers
2. 2. diastereomers
Enatiomers: the optical ismoers which posseses non superimposable mirror
image of each other.
It must contain atleast one chiral or asymmetric center.
Enantiomers molecule that have one carbon with four diff substituent have
non superimposable mirror image.
I,II,III and IV are four stereoisomers of 2,3-dibromopentane.
I and II are enantiomers.
III and IV are also enantiomers
What is relation between I and III; or I and IV; or II and III; or II and IV?

All these pairs are diastereomers, stereoisomers which are not mirror - image of each other are called
diastereomers.
Therefore,
I and III are diastereomers
I and IV are diastereomers
II and III are diastereomers
II and IV are diastereomers
A compound with two or more asymmetric carbon atom but having a
plane of symmetry ( mirror plane).
Meso means Middle which is inactive
if any conformer has plane of symmetry and the compound will be
achiral and an achiral compound with 2 chirality centre.
DRAWING OF ENANTIOMERS
 PERSPECTIVE: (Flying wedge)
Two of the bonds to the chirality center in the plane of the paper.
One bond s Solid wedge coming out of the paper (towards the viewer) and
another is hedged wedge projecting back from paper.
These two (hatched and solid wedge ) bond should be adjacent to each other
and should not be drawn between them.
FISCHER
Single dot for a bond that was slanted away from viewer.
Solid lines- directed towards the viewer.
Later victor mayer used the point of intersection of two perpendicular line to
represent chirality center.
Horizontal bond: towards the viewer
Vertical Bond: away from the viewer.
Horizontal line- bonds project out of the plane of paper towards the viewer.
Vertical: away from viewer.
 R-S-SYSTEM OF NOMENCLATURE
R,S-system of nomenclature was given by Cahn, ingold and Prelog in 1956. This is
called CIP rule.
In this system of nomenclature, Chiral, Carbon atom has either R or S configuration .
The configuration of the chiral carbon is decided as follow-
The four atoms or groups attached to the chiral carbon are ranked in order of priority
, priority is decided by following sequence rules [ CIP rule]
(a) Atom of higher atomic number gets priority. Atom of higher priority is assigned
no.1 & atom of least priority is assigned no.4.
I>Br>Cl>O>N>C>H
decreasing priority
(b) If the first atom of the two groups have same atomic number then relative
priority of the group is decided by a comparison of the atomic number of the next
atom in the two groups.
Ex.1—- In CH3 & –CH2–CH3
In both first atom is Carbon but next atom in –– CH 3 is H , while in ––CH2––CH3
, next atom is ‘C’. So ethyl group is given higher priority than methyl group.

Ex.2 — –CHO is given higher priority than –CN because in group image003 , C is
directly attached to oxygen while in –CN group C is directly attached to N. (at. no.
of oxygen is greater than N).

(c) Multiple bonds are treated as separate single bonds.

Ex.1—- –CH=O is given priority over –CH2OH

I>Br>Cl, OH>NO2>NH2>COOH>CHO>CH2OH
2. When priority of groups are decided by sequence rule then figure is viewed
from the group of higher priority to lower priority (2,3,4) & move your eye. If
eye moves in clock wise direction, the configuration is R (Rectus-Right) .If eye
moves in anti clock wise direction, the configuration is S (sinister – left).

3. When priority of groups are decided by sequence rule then figure is viewed
from the group of higher priority to lower priority (2,3,4) & move your eye. If
eye moves in clock wise direction, the configuration is R (Rectus-Right) .If eye
moves in anti clock wise direction, the configuration is S (sinister – left).
4) If the atom or group of lowest priority (i-e 4) occupies horizontal position
(right or left) in Fischer projection formula , then change the observed
configuration from R to S & vice versa.
Actual configuration is S-configurationClock wise , so
observed configuration is R configuration but Lowest priority
group i-e H lies on horizontal position therefore

In first chiral Carbon atom [C*] , Anti clock wise , so

observed configuration is S- configuration but Lowest priority
group i-e H lies on horizontal position therefore Actual
configuration is R-configuration
In second chiral Carbon atom [C*] , clock wise , so
observed configuration is R- configuration but Lowest priority
group i-e H lies on horizontal position therefore Actual
configuration is S-configuration

In both chiral Carbon atom [C*] , Anti clock wise , so

observed configuration is S- configuration but Lowest priority
group i-e H lies on horizontal position therefore Actual
configuration is R-configuration

configuration is R-configurationAnticlock wise , so

observed configuration is S- configuration but Lowest priority
group i-e H lies on horizontal position therefore Actual
Chirality:
Molecules which have handedness in reference to our each of which is
the non superimposable mirror image of the other.

It is observed that
Many (but not all) molecules that contain a chiral center are chiral.
Some molecules although contains chiral center yet are achiral.
Ex: Meso tartaric acid
An absolute configuration refers to the spatial arrangement of
the atoms of a chiral molecular entity (or group) and its
stereochemical description e.g. R or S, referring to Rectus, or
Sinister, respectively.

Relative configuration: The position of atoms or groups in space in

relation to (i.e., relative to) something else in the molecule. Cis, trans, E,
and Z are all designations of relative configuration.
 The eutomer is the
enantiomer having
the desired
pharmacological
activity, e.g., as an
active ingredient in a
drug.

The distomer, on the

other hand, is the
enantiomer of the
eutomer which may
have undesired
bioactivity or may be
bio-inert
GRANULOCYTOPENIA:
condition in which
there is a lower-than-
normal number of
granulocytes (a type
of white blood cell).
than
Compounds containing one chiral carbon atom:
A compound containing one asymmetric carbon atom is always optically
active and exists in 3 form ie +,- and both (dextro, levo or d/dl racemic).
Example:
Reactions of Chiral molecule:
The synthesis of chiral compounds from achiral to chiral always yields
the racemic modification.
Equimolar amounts racemic modification always optically inactive.

(Racemic mixture is optically inactive due to the fact that in

equimolecular mixture of enantiomeric pairs the rotation caused
by the molecules of one enantiomer is cancelled by the rotation
caused by the molecules of other enantiomer. ... )
RETENTION CONFIGURATION
F. RESOLUTION OF RAMEIC MIXTURE TOO
• Asymmetric synthesis is defined as synthesis of active optically active
product from optically inactive substrate with or without use of
enantiomers.
SAMP=(S)-1-amino-2-methoxymethylpyrrolidine
ENTGAGEN AND ZUSSAMEN
Z
A Newman projection visualizes the conformation of a chemical bond from front to back, with
the front atom represented by a dot and the back carbon as a circle. The front carbon atom is
called proximal, while the back atom is called distal.

Sawhorse Projection is a view of a molecule down a particular carbon-carbon bond, and groups
connected to both the front and back carbons are drawn using sticks at 120 degree angles.
Carbon atom at left of structure is considered to be close to the observer than Carbon at right.
In an eclipsed conformation the carbons are aligned so that the
hydrogens are lined up with each other. This creates steric hindrance
between them. In a staggered conformation the atoms are all equally
spaced from each other.
Skew conformation means it lies in between Staggered and Eclipsed.
Staggered and Eclipsed- Rotational isomers or Rotamers because they can
be converted into another by rotation of C-C bond.
Rotation of 600 convert staggered to eclipsed form.
The chair form shown to the right is the most stable conformation of
cyclohexane.

The C-C-C bonds are very similar to 109.5o, so they are almost free from angle
pressure.

It is also a completely staggered conformation, and is therefore free of

torsional stress.

Boat conformation is the least stable, with the highest strength, has steric
hindrance on carbon 1 and carbon 4 between the two equatorial hydrogens,
and has torsional stress, as each bond almost fully ellipses other bonds in the
Newman projection.
 Stereoisomerism in biphenyl compounds (Atropisomerism)
Biphenyls are compounds whereby a phenyl ring is connected to another
through a central σ bond.
In unsubstituted biphenyl, there is sufficient amount of freedom of
rotation around the central single bond to allow for free interconversion
between the various conformers or rotamers so that the various rotamers
cannot exist independently

PIVOT BOND

But biphenyls with large substituents at the ortho positions on either side of the central
σ bond experience restricted rotation along this bond due to steric hindrance. If the
substituents are different, a chiral molecule existing as a pair of enantiomers called
atropisomers.
 Polynuclear aromatic systems such as binol also exist as enantiomers.

Atropisomerism are stereoisomers as a result of restricted rotation about a

single bond.
Atropisomers are stereoisomers resulting from hindered rotation about
single bonds where the steric strain barrier to rotation is high enough to
allow for the isolation of the conformers.
Bulky substituents or strained rings may enhance the barrier to rotation
between two distinct conformations to such an extent as to allow
observation of atropisomers.
Atropisomerism is also called axial chirality and the chirality is not simply a
centre or a plane but an axis.

Biphenyl substituted on ortho position, which contains a chiral axis along the biphenyl linkage. The
biphenyl rings are perpendicular to each other in order to minimize steric clashes between the four
ortho substituents meaning that rotation about the biphenyl bond through pivotal bond is restricted
 Requirements for Atropisomerism:
1. A rotationally stable axis
2. Presence of different substituents on both sides of the axis
3. The configurational stability of axially chiral biaryl
compounds is mainly determined by three following factors:
i. The combined steric demand of the substituent in the
combined steric demand of the substituents in the proximity
of the axis.
ii. The existence, length and rigidity of bridges.
iii. Atropisomerisation mechanism different from a merely
physical rotation about the axis, e.g. photo chemically or
chemically induced processes.
 STEREO CHEMICAL ASSIGNMENT:
1. Determining the axial stereochemistry of biaryl atropisomers can be
accomplished through the use of a Newman projection along the axis of
hinderedrotation.
2. The ortho, and in some cases meta substituents are first assigned
priority based on Cahn–In gold–Prelog priority rules.
3. Starting with the substituent of highest priority in the closest ring
and moving along the shortest path to the substituent of highest priority
in the other ring, the absolute configuration is assigned P for clockwise
and M for counter clockwise
SAME PLANE: UPPER BELOW (SUB)
FRONT SIDE: THICK LINE
 STEREOSPECIFIC REACTIONS
A→B
C→D
WHERE A,B,C AND D ARE STEREOISOMERS.

STEREOSELECTIVE REACTIONS
A→B + C
WHERE A,B,C ARE STEREOISOMERS.
 Cis 2%

H2 AND
Pd 98%

Trans Cis-2-butene
2% 98%
 STEREOSPECIFIC REACTIONS:
These are the reactions in which stereochemically different reactants give
stereochemically different products.