ISOMERISM

Types of Isomerism.

(1) Structural isomerism.

When two or more compounds possess the same
molecular formula but different structural
formulae.

(2) Stereoisomerism.
Existence of the two or more compounds with the same
molecular and structural formulae, but different spatial
arrangements of atoms or groups is termed
stereoisomerism.
 Stereochemistry refers to chemistry in
three dimensions.
Stereochemistry.
Stereoisomerism.
Stereoisomers are divided into
two groups

•conformational isomers
•configurational isomers
 CONFORMATIONS

Different arrangements of atoms of a

molecule of definite structure that
can be converted into one another
by rotation about single carbon-carbon
bonds are called conformations.

The cause of rotation is

torsional strain.
Is it unable to bend or be forced out of
shape; not flexible, rigid?
The energy required to rotate the ethane
molecule about the carbon-carbon bond is
called torsional energy.
The infinity of intermediate conformations are called
skew conformations.
 Newman
projections
 Rotation is not quite free: there is an energy barrier.
The potential energy of the molecule is at a minimum for the
staggered conformation, increases with rotation, and reaches a
maximum at the eclipsed conformation.
 Most ethane molecules, naturally, exist in
the most stable, staggered conformation; or,
any molecule spends most of its time in the
most stable conformation.
The two sets of orbitals in ethane
tend to be as far apart as possible-
to be staggered.
 Conformations of n-butane
Van der Waals repulsion.
Due to the presence of the methyl groups,
there are several different staggered conformations
Any two atoms (or groups) that are not bonded to
each other can interact in several ways, depending on
their size and polarity, and how closely they are
brought together.
These non-bonded interactions can be either
repulsive or attractive, and the result can be either
destabilization or stabilization of the conformation.
 I II III
I-Anti conformation , II and III-Gauche conformations

There are two gauche conformations, II and III, in which

the methyl groups are only 60° apart. Conformations II
and III are mirror images of each other, and are of the
same stability; nevertheless, they are different.
Potential energy changes during rotation
about the C(2)-C(3) bond of n-butane.
Newman projection
 The anti conformation, is more stable
(by 0.8 kcal/mol) than the gauche.
Both are free of torsional strain.
But in a gauche conformation, the
methyl groups are crowded together,
and the molecule is less stable because
of van der Waals strain
(or steric strain).
 ջրածնական կապ

Hydrogen bond
 CONFORAMATION OF CYCLIC
ALIPHATIC COMPOUNDS.
BAEYER STRAIN THEORY

According to Bayer theory, when carbon is

bonded to four other atoms, the angle between
any pair of bonds is the tetrahedral angle 109.5°.
Any deviations from the "normal" bond angles
are accompanied by angle strain. So, in
cyclic compounds simultaneously coexist:

• angle strain which working

• torsional strain together or opposing
• van der Waals repulsion each other,
determine the net
stability of a
conformation.
Cyclopropane – plane, angle is 60°.
cyclopropanes are highly strained
because of torsional strain (eclipsed C-H
bonds on adjacent carbons) and angle
strain (bond angle compressed from
109.5° to 60°).

90°

Cyclobutane: rapid transformation between

equivalent non-planar "folded" conformations.
 108◦

CH2

CH2
H2
Planar cyclopentane: much
torsional strain. The molecule is
actually puckered, as “envelope”
120◦
chair hemichair Z- or -twist hemichair chair

chair hemichair
boat
Chair conformation Boat conformation Twist-boat conformation
Conformations of cyclohexane that are free of angle strain
(˜110.8◦).
 axial
equatorial
The chair form.
2
 EQUATORIAL AND AXIAL BONDS IN
CYCLOHEXANE
The bonds holding the hydrogens that are in the plane of the
ring lie in a belt about the "equator" of the ring, and are called
equatorial bonds.
Chair
cyclohexane:

equatorial and axial bonds

The bonds holding the hydrogen atoms that are
above and below the plane are pointed along an axis
perpendicular to the plane and are called axial
bonds.
 The chair form.
If we sight along each of the carbon-carbon bonds in
turn, we see in every case perfectly staggered bonds:

Staggered cyclohexane ethane

Chair
The chair conformation is a good deal
more stable than the boat conformation.
 Inversion of ring

e
a
The boat conformation
 Sighting along
either of two
carbon-carbon
bonds,
we see sets of
exactly eclipsed
bonds
 The boat conformation.
The considerable torsional strain:
as much as in two ethane molecules.

Eclipsed cyclohexane ethane

Boat
In addition, there is van der Waals strain due to crowding
between the "flagpole" hydrogens.
 Configurational isomerism
includes two types of isomerism:
✓Optical Isomerism. The necessary structural
feature of such type of compounds is the
presence of asymmetric carbon atom
(chiral centre).

✓Geometrical Isomerism (cis-trans isomerism) - due

to difference in spatial arrangements of the groups
(atoms) about the doubly bonded carbon atoms
(π-diastereomers)
Geometrical Isomerism (cis-trans isomerism)

H3C CH3 H3C H

C= C C= C
H CH3
H H
cis-2 Butene (b.p. 277 K) trans -2-Butene (b p. 274 K)
 Most biochemical reactions are catalyzed by
enzymes. The enzyme fumarase, for example,
³ µ
catalyzes the hydration of fumaric acid to malic
acid in apples and other fruits, Krebs cycle.
chirality

mirror
spiral staircase

In geometry, an
object that is not
superposable on
its mirror image
is said to be
dissymmetric.
 In chemistry, the word that corresponds to
dissymetric is chiral, as in a chiral
molecule.
A molecule that has any element of
symmetry, such as a plane, axe or a center of
symmetry is superposable on its mirror
image, is achiral.
Molecular chirality. Optical Isomerism .
The stereogenic
(chiral) center(s)

CHO CHO
H – C – OH HO – C – H
CH2OH CH2OH
D(+8.7) L(- 8.7)
Enantiomers.
 Mirror
images

L D
Enantiomers.
 The two mirror-image forms are
enantiomers of one another and are
not superposable.

2 nrule for the number of existing

isomeric structures will apply.
 Fischer projection formulas.
(stereochemical information in an abbreviated form ).
A projection of the chiral carbon onto the page is a
cross. It is customary to orient molecules with
several carbons so that the carbon chain is vertical,
the more oxidized carbon on the top.

D L
 Nomenclature for Chiral Molecules
Two systems are in common use today: the so-called D,L
system and the (R,S) system.

The assignment of L and D and (R) and (S) notation for glyceraldehyde.
 PHYSICAL PROPERTIES OF
ENANTIOMERS
The usual physical properties are identical for
both enantiomers of a chiral compound, but the
direction of rotation of polarized light plane
(equal numerically but opposite).
The term chiral recognition has been coined to refer to
the process whereby some receptors, enzyme or reagent
interacts selectively with one of the enantiomers of a
chiral molecule.
Very high levels of chiral recognition are
common in biological processes.
 Properties of chiral molecules:
optical activity.

A substance which causes the plane of

polarized light to undergo a rotation
is said to be optically active.
Optical activity is a physical property of a substance, just as
melting point, boiling point, density, and solubility are and is
measured by using an instrument called a polarimeter.

Unpolarized The polarizer plane-polarized

light from source light
 When the substance is chiral and one
enantiomer is present in excess of the
other, then the plane of polarization is
rotated through some angle a.

Plane-polarized Solution of a chiral substance Plane of polarization

light in which more of one enantiomer has undergone
than the other is present a rotation.
 Mixtures containing equal
quantities of enantiomers are
called racemic mixtures and are
optically inactive

All achiral substances are

optically inactive.
 *The sign and the magnitude of rotation
could be determined only experimentally
Rotation of the plane of polarized light in the clockwise
sense is taken as positive (+),
or dextrorotatory (d)
rotation in the
anticlockwise sense is taken as a negative (-) rotation
or levorotatory (l).
The enantiomers of 2-butanol were called:
the dextrorotatory form: d-2-butanol
the levorotatory form: l-2-butanol
a racemic mixture: dl-2-butanol
Current custom favors using algebraic signs instead, as in
(+)-2-butanol, (-)-2-butanol, and (±)-2-butanol,
respectively.
 Displaying Molecular Shapes.
Absolute and relative configuration.
The precise arrangement of substituents at a
chiral center is its absolute configuration.
Neither the sign nor the magnitude of
rotation by itself provides any information
concerning the absolute configuration of a
substance.

(+)-2-Butanol (-)-2-Butanol
?
 Absolute configuration.
Three-dimensional shapes of molecules are
determined by X-ray crystallography, a
technique that allows to "see" molecules in a
crystal using X-ray waves.
Molecular shape is critical to the proper
functioning of biological molecules.
The tiniest difference in shape can cause
two compounds to behave differently
or to have different physiological
effects in the body.
 Relative configurations
of all the compounds had experimentally
determined, compare with the absolute
configuration of
•a salt of (+)-tartaric acid
•D- and L- glyceraldehyde`s
configurations, which were previously
determined.
 Molecules with multiple stereogenic
centers.
Many naturally occurring compounds
contain several stereogenic centers. The
maximum number of stereoisomers for a
particular constitution is 2n,
where n is equal to the number of
stereogenic centers.
The best examples of substances with
multiple stereogenic centers are the
carbohydrates.
For compounds with more than one chiral carbon, quantity of
isomers are fewer than the maximum number of stereoisomers
if there are elements of symmetry.

I II III IV
Isomers I and II are nonsuperposable mirror images of one
another; i.e., they are enantiomers, but Isomers III and IV
are identical (plane of symmetry). Note: there are
only 3 stereoisomers for tartaric acid.
3 isomers only
!!!!!!
mesotartaric acid
A compound such as this unique isomer of tartaric
acid is called a meso compound.
Meso compounds are characterized by;
• an internal reflection plane, that is, one-half of
the molecule reflects the other,
•each chiral carbon has the same set of four
different substituents
•the number of stereoisomers is then less than 2n
For meso-tartaric acid this set is
-H, -OH, —COOH, and –CHOH-COOH.
 Remember!

Chiral center (asymmetric carbon)

containing compounds reveal
optical activity if there is NO any
element of symmetry in the
structure ( plane, axis or center).
 Diastereomers.
Stereoisomers that are not related as an
object and its mirror image are called
diastereomers and are not enantiomers.
Enantiomers must have equal and opposite specific
rotations.
Diastereomeric substances can have
different rotations, with respect to
both sign and magnitude.
When the carbon chain is vertical and like substituents are on
the same side of the Fischer projection, the molecule is
described as the erythro diastereomer.

COOH
COOH COOH COOH
COOH
H – CH– –OH
C – OH HO – C – H H – C – OH
H – C – OH
H–C
HO––OH
C–H H – C – OH HO – C – H
H – C – OH
COOH
COOH
COOH COOH COOH

I II III
erythro threo threo
When like substituents are on opposite sides of the Fischer
projection, the molecule is described as the threo
diastereomer.
 a hexose

Since there are four stereogenic centers

and there is no possibility of meso forms,
there are 24, or 16, stereoisomeric hexoses.
All 16 are known, having been isolated
either as natural products or as the
products of chemical synthesis.
D-glucose D-mannose D-fructose

epimers