Stereochemistry

Dr. Arabinda Chakraborty

❖ The part of science with deals with structure in three dimensions is called Stereochemistry

❖ Different compounds which have the same molecular formula are known as isomer; and
the phenomenon is known as 'isomerism'

❖ The isomers which have the same structural formula but differ in the spatial arrangement of
various substituent atoms or groups are called stereoisomers and phenomenon is known
as stereoisomerism

Types of isomerism

1. Structural/constitutional isomerism,
is a form of isomerism in which molecules
with the same molecular formula have
different bonding patterns and atomic
organization
2. Stereoisomer: Stereoisomers are isomeric molecules that have the same molecular
formula and sequence of bonded atoms (constitution), but differ in the three-dimensional
orientations of their atoms in space
a. Configurational stereoisomers: The stereoisomers which are non-interconvertible by
rotation around single bonds

These isomers may further be divided into two parts :

i. Geometrical isomers (also known as cis-trans isomerism or E-Z isomerism)

ii. Optical isomers (Enantiomers)

Geometrical Isomerism

Geometrical isomerism (also known as cis-trans, E-Z isomerism) is a consequence of the

spatial geometry associated with double bond which restricts rotation about it

Two methyl groups are on the same Trans isomer has the methyl groups on
side of the double opposite sides of the double bond
 E and Z system of nomenclature of geometrical isomers

✔ When, there are three or four different atoms or groups attached to the carbon atoms of
a double bond, it is difficult to assign cis or trans designation to the geometric isomers

✔ To eliminate this confusion, a more general system for designating configuration about a
double bond has been adopted

✔ This method, which is called the E and Z system, is based on a priority system originally
developed by Cahn, Ingold and Prelog for use with optically active substances

The following simple steps need to be followed for specifying the configuration

A. Assign a priority number 1 or 2 to groups on each carbon atoms of the double bond

(ii) Compare the priority of groups (or atom) at one carbon relative to the other
(iii) The configuration is represented as Z (German; Zusammen-together) if both the first
priority groups are on the same side of the double bond
(iv) If the first priority groups are on opposite sides of the double bond, the configuration
is E (entgegen-across)
 Atoms or groups are assigned priority by the following rules

(a) Substituents are listed in order of decreasing atomic number of the atom directly
joined to the carbon

(b) Higher priority is assigned to atoms (directly attached to the carbon atom) of higher
atomic number

(c) Where two or more of the atoms connected to the asymmetric carbon are the same,
the atomic number of the second atom determines the order

(d) If isotopes of the same element are attached, the isotope with higher mass number
will have a higher priority

(e) If the priority cannot be decided by rule, it is then determined by comparing the next
atoms in the group and so on

I > Br > Cl > S > O > N > C > H

 (f) A doubly or triply bonded atom is considered equivalent to two or three such
atoms. Thus a carbonyl group is considered as if, carbon had two single bonds to
oxygen, i.e.,

Example: Let us consider an' example of an alkene in which one of the doubly
bonded carbon atom has Br and I and the other has F and Cl Since I has a higher
atomic number than Br, it is assigned higher priority; Similarly CI is of higher priority
than F in the second olefinic carbon atom.

Thus it is the E and Z configurations of the two isomers of l-bromo-2-chloro-2

fluoro-I-iodo-ethene
 Optical Isomerism
✔ Certain compounds can exist in two stereoisomeric forms whose molecular
structures cannot be superimposed on one another
✔ Such a pair of compounds is known as optical isomers and phenomenon as optical
isomerism
✔ The physical properties of such isomers are identical, e.g., they have the same
melting points, boiling points, etc
✔ Solutions of certain organic compound when placed in the path of plane polarised
light, rotate the plane of polarisation to a certain fixed angle
✔ This property of rotating plane of polarisation is known as optical activity and such
compound are said to be optical active
✔ The substances which rotate the plane-polarized light to the right or clockwise are
called dextro rotatory
✔ Those which rotate to the left or anticlockwise are called levo rotatory
✔ The substances which do not rotate the plane-polarized light either way are said to
be optically inactive
 Optical activity
An optically active compound is one which rotates the plane of polarization

If from the vantage point of the observer the rotation is in the clockwise direction,
the sample is said to be dextrorotatory. The angle of rotation, α, is considered to be
positive (+)

If the rotation is in the counterclockwise direction, the sample is said to be

levorotatory and the angle, α, is then negative (-)

There is no correlation between (+)/(-) and (R)/(S). Thus (R)-2-chlorobutane is the

levorotatory enantiomer

Polarization is a property applying to transverse waves that specifies the

geometrical orientation of the oscillations. An electromagnetic wave such as light
consists of a coupled oscillating electric field and magnetic field which are always
perpendicular and also perpendicular to the direction of motion of the wave.
By convention, the "polarization" of electromagnetic waves refers to the direction of
the electric field. In plane polarization, the fields oscillate in a single plane. (next page)
Plane-polarized light is produced by passing normal light through a polarizer.

• When plane-polarized light passes through a solution of achiral molecules,

the light emerges from the solution with its plane of polarization
unchanged.
However, when plane-polarized light passes through a solution of a chiral compound,
the light emerges with its plane of polarization changed.

• Optical Activity – The ability of a compound to rotate the plane of polarized

light.
• A compound that rotates the plane of polarization is said to be optically
active.
• Chiral compounds are optically active and achiral compounds are optically
inactive.
• A polarimeter is used to make such measurements
 Counterclockwise
Clockwise
Levorotatory (-)
Dextrorotatory (+)
 CHIRALITY
Molecules that are not superimposable on their mirror images are chiral (Greek,
Cheir, 'handedness')
Achiral objects can be superimposed on their mirror images
There is close relationship between chirality and optical activity
Chirality in molecules is due to the presence of an sp 3 carbon atom with 'our
different groups attached to it

Such a molecule has no plane of symmetry (a plane of symmetry divides a molecule

in such a way that one half is the mirror image of the other half) and exists as a pair
of enantiomers

A chiral carbon is the one" in which all the four substituents are different. Such
carbon atom is sometimes also referred to as asymmetric carbon atom
 Asymmetric centers

An asymmetric center is an atom that is bonded to four different groups

 Chirality
❑ Chiral – Non superimposable on its mirror image
❑ Achiral – Superimposable on its mirror image
❑ An object is chiral if its mirror image is different
from the original object
 Plane of Symmetry
It is an imaginary plane by which if we bisect a molecule in such a way that one half
becomes the mirror image of the other, then the molecule is said to possess a plane
of symmetry.
Planes of Symmetry

A molecule that has a plane

of symmetry is achiral

• Cis-1,2-dichlorocyclohexane is
achiral because the molecule
has an internal plane of
symmetry

• Both structures above can be

superimposed (they are
identical to their mirror images)
 Centre of symmetry
A point in the centre of the molecule is a center of symmetry if a line drawn from it to
Some element, when extended an equal distance in the opposite direction,
encounters an identical element

The blue point is an inversion centre of the molecule. The operation of inversion (i)
involves the projection of each atom onto a point at the center of the molecule,
followed by movement through the point to a distance equal to the projection distance.
 Requirement of optical activity

i. The only necessary, inflexible, and sufficient condition to exhibit optical activity is
that the geometrical structure should not superimpose on its mirror image
ii. Superimposability can be verified with the help of symmetry elements- plane,
centre and axis of symmetry
iii. The molecule lacking all symmetric elements is called asymmetric and is optically
active and can form non superimposable mirror image
iv. It has been observed that molecules lacking plane and centre of symmetry are
also optically active
v. Such molecules are called dissymmetric molecules. Thus all asymmetric
molecules are dissymmetric, but the reverse is not true. However, both of them
are optically active.
Optical rotation is dependent on concentration, path length, temperature, and the
wavelength of light used, as well as the solvent.

Specific Rotation
The specific rotation of a molecule is the rotation in degrees observed upon passing polarized light
through a path length of 1 decimetre (dm) at a concentration of 1 g/mL. Specific rotation is almost
always reported along with the temperature, wavelength of light used, the solvent, and the
concentration, since it is sensitive to these factors as well.

Specific Rotation [α]λt : a standardized value for the optical rotation

Observed rotation depends on the length of the cell and concentration, as well as the strength of
optical activity, temperature, and wavelength of light

Where α (observed) is the rotation observed in the polarimeter, c is concentration in g/mL, and l is
length of sample cell in decimeters, t temperature, λ wavelength of light
 Enantiomerism

✔ Isomers whose structures differ only in being mirror-images of each other (non
superimposable mirror image)
✔ Have identical physical properties (boiling point, melting point, and density)
✔ Rotate the plane of polarized light in the same magnitude, but in opposite directions

✔ Such isomers are called enantiomers and phenomenon is known as enantiomerism

✔ The enantiomers react at different rates and form products in different amounts in
asymmetric environment

✔ They act at different rates, if anyone of the reagent solvent or catalyst is chiraI

✔ A substance composed of equimolecular amounts of a pair of enantiomers is a

racemic modification
Enantiomers of Tartaric acid
 Diastereomers
Stereoisomers that are not mirror images of each other are called diastereomers.
Stereoisomer I and II , III and IV is enantiomers

I and III are diastereomers

 Fischer Projections
Planar representation of a 3-D structure of a molecule

Chiral carbon is at the intersection of horizontal and vertical lines

▪ The molecule is oriented in such a way that longest carbon must be present
vertically with most oxididisable group at the top.
- COOH > -CHO > - CH 2OH
▪ Vertical lines represent bonds going away from the observer i.e., behind the plane
of the paper.
▪ Horizontal lines represent bonds coming towards the observer i.e., above the
plane of paper.
 Relative configuration (D/L)
▪ The molecule is oriented in such a way that longest carbon must be
present vertically with most oxididisable group at the top.
- COOH > -CHO > - CH 2OH
▪ If H atom is present at the right hand side and other foreign atom/group
(e.g., - OH) placed at the left hand side then the carbon centre is
designated as L.
▪ If H atom is present at the left hand side and other foreign atom/group
(e.g., - OH) placed at the right hand side then the carbon centre is
designated as D.

Consider bottom most chiral carbon

 R and S nomenclature
✔ With the help of this system we can know absolute configuration of the molecule

✔ Symbols R and S are derived from the Latin words rectus (right) and sinister (left)
✔ The nature of the groups is determined by the priority of the groups which depends
upon the following rules:
Rule 1: If the four atoms attached to the chiral center are all different, priority depends
on atomic number, with the atom of higher atomic number getting higher priority.

I > Br > Cl > S > F > O > N > 13C > 12C > 2H (D) > 1H

Thus, in bromochlorofluoroiodo methane, priority sequence of four atoms are I (Z = 53)

> Br (Z = 35) > CI (Z= 17) > F (Z = 9)

If two atoms are isotopes of the same element, the atom of higher mass number has

the higher priority

Rule 2: If two atoms attached to the chiral centre are the same, we compare the atoms
attach to each of these first atoms

Example, in sec-butyl chloride, in which two of the atoms attached to the chiral center
are themselves carbon. In CH3 the second atoms are H, H, H; in C2H5 they are C, H,

Since, carbon has a higher atomic number than hydrogen, C2H5 has the higher priority.
A complete sequence of priority for see-butyl chloride is therefore CI, C2H5, CH3, H

Rule 3: If there is a double or triple bond, both atoms are considered to be duplicated or
triplicated

Example : In glyceraldehyde the OH group has the highest priority of all, the O, O, H of -CHO takes
priority over the O, H, H of –CH2OH. The complete sequence is then -OH, -CHO,-CH2OH, -H
Assigning R and S Configuration to Fischer Projections
 Meso Compounds

When a non planar optical isomer is found to be optically inactive inspite

of the presence of multiple chiral centres, then the molecule is said to be a
meso compound.

⦿ Meso compounds have a plane of symmetry

⦿ If one image was rotated 180°, then it could be superimposed on the
other image
⦿ Meso compounds are achiral even though they have chiral centers
 meso tartaric acid: The groups on the top carbon
reflect (through the symmetry plane) onto the
groups on the bottom carbon

Meso compounds have two chiral centers, the configuration of compound

is either R,S or S,R,

They are optically inactive because rotation by one chiral centre is

compensated by second chiral centre

The compensation occurs within molecule, so, it is called internal

compensation

In case of recemic mixtures (50-50% mixture of enantiomers), the net

rotation is zero because rotation of one isomer is compensated by its
enantiomer, so, it is called external compensation.
 Racemic Mixtures

• Equal quantities of d- and l-enantiomers.

• Notation: (d,l) or (±)

• No optical activity.
• The mixture may have different boiling point (b. p.) and melting
point (m. p.) from the enantiomers!
 Conformation
Different arrangements of atoms that can be converted in to one another by rotation
about single bonds are called conformations
Evidently, such compounds are capable of existing in large number of isomeric
structures which are called rotational or conformational isomers or conformers

Conformational analysis of straight chain alkanes

• Conformational analysis is the study of how conformational factors affect the structure
of a molecule and its properties
• Rotation about single bond produces isomer that differ in conformation.
• Conformers have same connection, interconverts rapidly, thus cannot be isolated.
• Can be represented in 2 ways: sawhorse representation or Newman projection

sawhorse representation Newman projection

Torsion angle or dihedral angle is the angle between the H-C-C plane and the C-C-H
plane

Newman projection is important in alkane stereochemistry. A representation of the

conformation of a molecule in which the viewer's eye is considered to be visualizing
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. This type of representation
clearly illustrates the specific dihedral angle between the proximal and distal atoms
 Conformational analysis of ethane
Two conformational isomers or conformers.
• Only two conformers. Eclipsed form = all hydrogen atoms nearest to each
other
Staggered form = all hydrogen atoms are furthest apart
 n-Butane conformation
Consider the two central carbon atoms in the molecule.
6 different conformers can be formed by 60° rotation along central C2-C3 bond.

3
 Isomerism in transition metal compound
✔ The transition metals form a large number of complex compounds in which the
metal atoms are bound to a number of anions or neutral molecules
✔ In modern terminology such compounds are called coordination compounds
✔ Chlorophyll, haemoglobin are coordination compounds of magnesium and iron
✔ Variety of metallurgical processes, industrial catalysts and analytical reagents
involve the use of coordination compounds

Isomers
• Major Types
STEREOISOMERS
1) Geometrical isomerism 2) Optical isomerism

STRUCTURAL ISOMERS
1) Linkage isomerism 2) Coordination isomerism
3) Ionisation isomerism 4) Solvate isomerism
 Stereoisomers
Isomers that have the same bonds, but different spatial arrangements

1. Geometric isomers
Differ in the spatial arrangements of the ligands
Have different chemical/physical properties different colors, melting points,
polarity, solubility, reactivity etc.

Pt(NH3)2Cl2
cis-[Co(en)2Cl2]+
Enantiomers
(Non – superimposable)
 Structural Isomers

1) Ionisation Isomerism - Arises when the counter ion in a complex salt is itself a
potential ligand and can displace a ligand which can then become the counter ion
Example [Co(NH3)5SO4]Br and [Co(NH3)5 Br]SO4

2) Coordination isomers - Arises from interchange of ligands between cationic and

anionic entities of different metal ions present in a complex.
Example [Cu(NH3)4][PtCl4] and [Pt(NH3)4][CuCl4]

3) Linkage isomers - differ in the atom of a ligand bonded to the metal in the complex

Example [Co(NH3)5(ONO)]2+ and [Co(NH3)5(NO2)]2+

4) Solvate (Hydrate) Isomerism
also known as hydrate isomerism in case water is involved as solvent
similar to ionisation isomerism, differ by whether or not a solvent molecule
is directly bonded to the metal ion or merely present as free solvent
molecules in the crystal lattice.
Example
aqua complex [Cr(H2O)6]Cl3 (violet) and its solvate isomer
[Cr(H2O)5Cl]Cl2. H2O (grey green).