Stereochemistry

Stereochemistry:

It is branch of chemistry that involves the study of the

different spatial orientation or arrangement of atoms or groups
in the molecule.

This branch of chemistry is commonly referred to as 3-

Dimensional chemistry.

Since, it focuses on stereoisomers (i.e. chemical compounds

with same molecular formula but different spatial
arrangement in three dimensions).
Enantiomers - Non-superposable mirror images or chiral
molecules which are mirror images.

Enantiomers have identical: b.p.’s, m.p.’s, solubilities, index

of refraction, IR, NMR etc.

Chiral or asymmetric carbon - a tetrahedral carbon atom

bearing four different substituent’s.
Diastereomers - stereoisomers which are not enantiomers (or
mirror images), and not mirror images.

Diastereomers have different physical properties.

Racemic mixture - an equimolar (1:1) pair of enantiomers is

called a racemic mixture. A racemic mixture has an optical
rotation of zero.

Optical activity - the ability of chiral substances to rotate the

plane of polarized light by a specific angle

Device used to measure optical rotation: Polarimeter

Dextrorotatory (+): an optically active compound that rotates
plane polarized light in a clockwise direction.

Levorotatory (-): an optically active compound that rotates

plane polarized light in a counter clockwise direction.
Representation of three dimensional molecules

Configuration of a chiral molecule is three dimensional

structure and it is not very easy to depict on a paper having
only two dimensions.

To overcome this problem four 2dimesional structures known

as projections have been used.

(1) Dashed Wedge or Flying Wedge formula

(2) Fischer projection
(3) Sawhorse formula
(4) Newmann projection.
Dashed-Wedge or Flying Wedge formula

In this representation a solid continuous lines

represent bond is in the plane.

A solid wedge line represent bond is above the plane i.e.

towards the observer.

A broken wedge / dashed line represent the bond is below

the plane i.e. away from the observer.
Dash-Wedge formula
Fischer projection:

In this representation, bonds are drawn as solid lines. The

bonds are placed vertical and horizontal to each other.

A tetrahedral carbon is represented using just two crossed

lines represents the stereo center.
Horizontal line is coming out of the plane of the page
(towards observer) and vertical line is going back behind the
plane of the paper (away from observer).

In Fischer representation most oxidized carbon atom is placed

on the vertical line at the top.
In Fischer representation most oxidized carbon atom is
placed on the vertical line at the top.
Saw-horse representation

In this representation each carbon atoms may be viewed

as a letter “Y”.
Newmann Projections

In this representation the molecule is viewed along the bond

joining the two carbon atoms.

The front carbon shown by three solid lines i.e. “Y”

The rear carbon is shown by a circle with three bonds

pointing out from it i.e.
Combining the front and rear results in the eclipsed
Newmann projection which on rotation through 180o results
in stable staggered Newmann projection.
Configuration: Three dimensional arrangements of atoms or
groups around an asymmetric carbon atom or chiral centre are
known as configuration.

Two systems have been developed to study the configuration

of organic compounds.

Relative configuration (D-L configuration): Prior to 1951,

there was no method available for determining the absolute
configuration of a compound.

So, configuration relative to that of standard ((+)-

Glyceraldehyde) were determined. This system of
configuration is known as D-L configuration.
D-L Conventions:
D-L system is seldom used today except for some class of compounds
like carbohydrates and amino acids.

D- & L - Glyceraldehyde are used as standard references for D-L system

of configuration of carbohydrates.

D- & L - Alanine are used as standard reference for alpha amino acid
with D-L system of configuration.
D-series of sugars are those with –OH group attached to
highest numbered stereo center on the right side in
Fischer projection.
L-series are those with –OH group attached to highest
numbered stereo center on the left side in Fischer
projection.
D- & L- configuration of α-amino acid refers to the
configuration of the regardless of the number of asymmetric
carbon in the molecule.
The D- & L- system has the disadvantage of specifying
configuration of only one stereocenter.

D- & L- configurations are not related to the optical rotation

of sugars.
R-S system:

The Sequence (CIP) Rule is the actual method whereby the

four substituents on an asymmetric carbon may be assigned
priorities 1, 2, 3 or 4 so that the absolute configuration R or S
may be determined.

Rule-1: Rank the groups or atoms boned to the asymmetric

carbon in order of priority. Priorities depend on atomic
number; the atom of higher atomic number is assigned higher
priority.
If two atoms are isotopes of same element, the atom of
higher mass number has the higher priority.

Rule-2: If the relative priority of two groups can not be determined by

the first atom, then look for next atom, often it may be necessary to
proceed atom by atom till a point of difference is obtained.
Rule-3: In the case of double or triple bond, either atoms or groups are
considered as duplicate or triplicate.

Rule-4: Orient the molecule so that the groups or atoms with lowest
priority are directed away from the observer.

Rule-5: Draw an arrow from the group or atom with highest priority
to the group or atom with next priority (decreasing priority). If you
trace a circular path from 1 to 2 to 3 and the path describes a
clockwise rotation, then the center is called R (Latin: rectus means
right). If the path shows a counter clockwise rotation, then the
chiral center is called S (L.: sinister means left).

Note: If fourth group is above the plane, then clock wise movement
is “S”, while anti clock wise movement is “R”.
R-S nomenclature for Fischer projection:

Case-I: If the 4th group is present on top or bottom of the vertical line in the
Fischer projection.
Case-II: If the 4th group is present on left or right of the horizontal line I
n the Fischer projection.
Conversion of Dash Wedge formula to Fischer projection

If the solid lines are on right side in the first step solid line is
written vertical line.

In the second step horizontal line is drawn and substituent

which is placed on wedge bond will be placed on right side.
Finally look for whether the most oxidized carbon is placed on top of the
vertical line.

If not, then rotate the Fischer projection through 180o in the plane of
the paper.
If the solid lines are on left side in the first step solid line is written
vertical line.

In the second step horizontal line is drawn and substituent which is

placed on wedge bond will be placed on left side.
Conversion of Fischer projection to Dash Wedge formula

The reverse of the above discussed method will be used to

covert Fischer projection to Dash Wedge formula.

In this conversion first step is Fischer vertical line will be

written in solid line of Dash formula.

In the second step horizontal line will be written in dashed

line and wedge line.

To place the substituent on dash and wedge line configuration

of Fischer projection is used.
 Conformational Isomers

Isomers that differ as a result of sigma bond rotation of

C-C bond in alkanes
 Bond Rotation and Newman Projections

As carbon-carbon bond rotates, interconvert between

staggered and eclipsed conformers

Eclipsed conformer is 12.0 kJ/mol higher in energy

 Torsional Strain Energy

Force that opposes rotation due to the repulsion of

bonding electrons

We do not observe perfectly free rotation

There is a barrier to rotation, and some conformers are

more stable than others

Small energy barrier easily overcome at RT

Each eclipsed H-H costs 4 kJ/mol of Torsional Energy

 Strain Energy in Alkanes

Torsional Strain

Steric strain- repulsive interaction occurring between

atoms that are forced closer together than their atomic
radii allow
 Types of Strain

Angle strain - expansion or compression of bond

angles away from most stable

Torsional strain - eclipsing of bonds on neighboring

atoms

Steric strain - repulsive interactions between

nonbonded atoms in close proximity

RING STRAIN = combination of Angle Strain + Torsional

Strain
Conformations of Propane
Conformations of Butane
Two Different Eclipsed Conformations
Steric strain: Any type of repulsion between two closely
spaced non-bonded atoms or group of atoms is termed as steric
strain.

The repulsions between electrons of these closely spaced

atoms imparts a destabilising effect and is the major cause of
the overall strain in a molecule.

It can be classified into various types of strains as described

below.
Angle strain: If the angle between a pair of adjacent bonds on
a carbon atom is less than the tetrahedral angle (i.e., 109.5o)
then there is a destabilisation due to the bond pair - bond
pair repulsion.
Van der Waals strain: This type of strain arises when the
electron clouds of a pair of bulky groups are too close to each
other.

It leads to an increase in energy of the system due to the

electrostatic repulsion of the electron clouds.
Torsional strain: When a molecule is able to rotate around a
sigma bond, the other three bonds on each carbon holding
the single bond move relative to each other resulting in
different levels of torsional strain.

The relative movement of these bonds can be better

understood in terms of dihedral angle.

A dihedral angle (θ) is the angle between the two intersecting

planes formed by the bonds on adjacent carbon atoms.

The maximum strain is observed when these bonds are

closest to each other, i.e. in an eclipsing position (θ = 0°).

Hence this strain is also known as eclipsing strain.

With the rotation around the sigma bond, the dihedral angle
changes and consequently the repulsion between the bonded
pair of electrons (torsional strain) also changes.

The strain is minimum at θ = 60° (staggered conformation).

Ring strain: Generally, a ring or cyclic structure is less stable
than an equivalent acyclic structure, primarily due to angle
and torsional strain.

The extra energy is released when the ring is opened is known

as ring strain.
Conformation of Cyclohexane:

A planar structure of cyclohexane is clearly improbable.

The bond angle would be 120o i.e. 10.5o larger than the ideal
tetrahedral angle.

Every C-C bond in such structure would be eclipsed.

The resulting angle and eclipsing strain would severely

destabilize this structure.
If two carbon atoms on opposite side of six member ring are
lifted out of the plane, much of the angle strain can be
eliminated.

It can form Chair conformation or Boat conformation.

Chair conformation:

It is non planar puckered conformation.

All bonds are fully staggered therefore Pitzer strain is

minimized.

The bond angles are not exactly 109o.28’ but 111o.

Relative energy is zero (four carbons are planar, one puckered

up and one puckered down)
Cyclohexane forms a number of different conformers.

However, structure other than the chair conformation suffers

torsional strain, angular strain or both.
Boat Conformation:
Even though boat conformation is free from angular strain.

However, in addition to the torsional strain resulting from 4

H---H eclipsing interactions, it also has a flagpole interaction
between the hydrogen atoms on 1- and 4-carbon atoms.

Hence, it has higher energy than chair conformation of about

25 KJ/mol or 6.0 Kcal/mol.
The eclipsing interaction can be relieved by slightly twisting
two C-C bonds resulting in new conformation called twist boat
conformation.
Twist Conformation:

It is more stable than the boat conformation, but less stable

than than chair conformation. The flagpole interactions and
torsional strain in the boat conformation are reduced in the
twist conformer.

The twist boat has energy of about 21 KJ/mol or 5.5 Kcal/mol

which is lower than boat conformer.
Half chair conformation:

It is a transition state conformation.

The half chair conformer lies about 43 KJ/mol or 10 Kcal/mol

above chair conformation.

It has five carbons lie in plane and one puckered out of plane.
Stability order of cyclohexane conformers:

Chair > Twist boat > Boat > Half chair

Careful examination of cyclohexane allow us to find that the
twelve hydrogens are not structurally equivalent.

Equatorial Bonds: These are three sets of two parallel bonds,

each of which are parallel to two of the bonds in the ring.

Equatorial bonds alternate from slightly up to slightly down

orientation on moving from one carbon to the next.
Axial Bonds: They are parallel to each other and to the
principal axis, but perpendicular to the average plane of the
ring.

There are three bonds facing up and three facing down.

An inversion of a cyclohexane chair involves all of the
conformations of cyclohexane
Starting with a chair conformation a, cyclohexane first passes through a “half-chair”
conformation b.

The half-chair, as expected, has a very high energy and is only a transition state, which
gives rise to the actual conformation—twist-boat c.

Next, the twist-boat conformation flips into the alternative twist-boat conformation e.

The transition state for this flip is the boat conformation d.

Then, the cyclohexane molecule passes through another half-chair transition state f
(mirror image of the first one) and finally arrives at the alternative chair conformation
g.

At room temperature cyclohexane interconvert from one chair form to another

referred to as ring inversion or ring flipping.
Axial and equatorial bonds also undergo interconversion,
when a chair conformation flips to the other.

However, their relative orientations in space do not change.

Since two equilibrium chairs are in rapid equilibrium all

twelve hydrogen have 50% equatorial and 50% axial
character.
In boat conformation there are four types of hydrogens

1. Flag pole hydrogen – 2 Nos (Hfp)

2. Bow spirit hydrogen – 2 Nos (Hbs)
3. Quasi axial hydrogen – 4 Nos (Hqa)
4. Quasi equatorial hydrogen – 4 Nos (Hqe)
 Conformations of Cycloalkanes

Molecules show strain arising out of non-ideal geometry.

The internal energy of the molecule is dependent on several factors.

Total strain energy = 1 + 2 + 3 + 4

1 = stretching and compression of bonds (bond strain)

2 = Bond angle distortion (Baeyer strain, classical strain)
3 = Tortional strain (eclipsing strain)
4 = steric strain (vander waals strain)

A molecule will adopt the geometry, that minimises its total

strain energy.
 ELEMENTS OF SYMMETRY

Elements of symmetry offer a simple device to decide

whether a molecule is chiral or achiral, i.e., whether it is
superimposable on its mirror image or not.

When a molecule has no plane of symmetry, no centre of

symmetry and no alternating axis of symmetry, it is non
superimposable on its mirror image and is chiral (optically
active).
 PLANE OF SYMMETRY

The plane which divides a molecule in to two equal halves

which are related as object and mirror image is known as
plane of symmetry.

The molecules having plane of symmetry are achiral

(optically inactive).
 CENTER OF SYMMETRY

A center of symmetry in a molecule is said to exist if a line is

drawn from any atom or group to this point and when
extended to an equal distance beyond this point, meets the
identical atom or group.

All lines are passing through this point, hence it is the center
point of the molecule.

A centre of symmetry is usually present only in an even

number ring.

For example, the molecule of trans -2,4-dimethyl-cyclobutane

–trans-1,3- dicarboxaylic acid has a center of symmetry.
All lines are passing through this point, hence it is the center point of
the molecule)
Another interesting example is dimethyl ketopiperizine.

This has two isomers, cis and trans.

The cis form has no plane of symmetry or centre of symmetry.

The trans form on other hand, has a centre of symmetry.