Isomerism
Same molecular formula, different connectivity of
atoms or different arrangement in space.
Mukesh Paradiya
M Tech IIT Bombay
Structural or constitutional isomers
• Compounds with same molecular formulae, whose atoms are connected differently, are
called constitutional or structural isomers
• Constitutional isomers are always different compounds with different properties but with
the same formula.
Chain isomers
Functional isomers
Positional isomers
Importance of stereoisomers
That interactions between molecules in
the biological world are highly stereo-
selective is not surprising, but just how
these interactions are accomplished at
the molecular level with such precision
and efficiency
Cis-platin (Figure a) is a widely used anticancer drug , but the trans-
platin (Figure b) is ineffective in fighting cancer.
Conformational isomers (Conformers)
• Conformation: Any three-dimensional arrangement of atoms in a molecule that results from
rotation about a single bond.
• Sawhorse representation views the carbon–carbon bond from an oblique angle and indicates
spatial orientation by showing all C - H bonds.
• Newman projection: A way to view a molecule by looking along a carbon-carbon single bond
to help evaluate the relative orientations of attached groups.
Conformational isomerism in ethane:
• Staggered conformation: A conformation about a carbon-carbon single bond in which the
atoms or groups on one carbon are as far apart as possible from atoms or groups on an
adjacent carbon.
• Eclipsed conformation: A conformation about a carbon-carbon single bond in which the
atoms or groups on one carbon are as close as possible to the atoms or groups on an
adjacent carbon
Dihedral angle or Torsional angle: The angle created by two intersecting planes.
Torsional strain: Strain that arises when nonbonded atoms separated by three bonds are forced
from a staggered conformation to an eclipsed conformation. Torsional strain is also called
eclipsed interaction strain.
Energy diagram of ethane conformers: The energy of ethane as a function of dihedral angle.
The eclipsed conformations are approximately 12.6 kJ (~3.0 kcal)/mol higher in energy than
the staggered conformations.
Ethane molecule spends most of the time in staggered conformation and only small amount of
time it spends in eclipsed conformation
It has not been possible to separate and isolate different conformational isomers of ethane as
they interconvert rapidly.
Conformational isomerism in butane:
• Gauche conformation: A conformation about a single bond of an alkane in which two bulky
groups on adjacent carbons lie at a dihedral angle of 60°.
• Anti conformation: A conformation about a single bond in which two bulky groups on
adjacent carbons lie at a dihedral angle of 180°.
Steric strain is the repulsive
interaction that occurs when
atoms are forced closer together
than their atomic radii allow. It’s
the result of trying to force two
atoms to occupy the same
space.
As rotation continues, an energy minimum is reached at the staggered conformation where the methyl
groups are 60° apart. Called the gauche conformation, lies higher in energy than the anti conformation even
though it has no eclipsing interactions. This happens because the hydrogen atoms of the methyl groups are
near one another in the gauche conformation resulting in steric strain.
Cis/Trans or Z/E- or Geometrical isomerism
For rotation to occur around a double bond, the p bond must break and re-form (Figure 7-2).
Thus, the barrier to double-bond rotation must be at least as great as the strength of the pi bond
itself. Hence, no conformational isomers.
• The two methyl groups in 2-butene can either be on the same side of the double bond or
on opposite sides.
• Since bond rotation can’t occur, the two 2-butenes can’t spontaneously interconvert; they
are different, isolable compounds.
• Cis–trans isomerism can occur whenever both double-bond carbons are attached to two
different groups.
• If one of the double-bond carbons is attached to two identical groups, then, cis–trans
isomerism is not possible
Exercise
The method used for describing tri or tetra substituted-alkene stereochemistry is called the E,Z
system and employs the same Cahn–Ingold–Prelog sequence rules
Exercise
Properties of cis/trans isomers
Cis alkenes are less stable than their trans isomers because of steric strain between the two
larger substituents on the same side of the double bond.
Cis–trans interconversion of alkene isomers does not occur spontaneously, but it can be done
by treating the alkene with a strong acid catalyst. If we interconvert cis-2-butene with trans-2-
butene and allow them to reach equilibrium, 76;24 ratio of trans/cis is formed because the trans
isomer of 2-butene is more stable than the cis isomer by 2.8 kJ/mol at room temperature.
Melting point: Trans-isomer has higher MP than cis due to efficient packing.
Boiling point: Cis-isomer has higher BP than trans due to polarity. Cis polar, trans-nonpolar
Heat of hydrogenation:
• More energy is released in the hydrogenation of the cis isomer than the trans isomer
because the cis isomer has more energy to begin with.
• Alkenes follow the stability order:
Reason: hyperconjugation and stronger sp3C-sp2C bond
Cis–Trans Isomerism in Cycloalkanes
Stereoisomerism and chirality
When you hold a left hand up to a mirror, the image you see looks like a
right hand. if you have a ring on the little finger of your right hand, your
mirror image has the ring on the little finger of its left hand. If you part
your hair on your right side, it will be parted on the left side in your
reflection. You and your reflection are different objects. You cannot
exactly superpose one on the other.
Chiral
• Chiral objects or molecules: Objects that are not superposable on their mirror images are
said to be chiral OR a molecule that is not identical to its mirror image
• Chiral objects: left hand or right hand, a spiral binding on a notebook, a machine screw with a
righthanded thread, a ship’s propeller.
• They do not have center of symmetry.
Achiral
• Achiral : An object that lacks chirality. They have plane or center of symmetry.
• A plane of symmetry is an imaginary plane passing through an object or a molecule dividing
it such that one half is the reflection of the other half
• Achiral objects: Coffee mug, a regular tetrahedron, a cube, and a perfect sphere
• Centre of symmetry: A point so situated that identical components of an object are located
on opposite sides and equidistant from that point along any axis passing through it.
Enantiomers
Enantiomers: Stereoisomers that are nonsuperposable mirror images of each other. It refers to a
relationship between pairs of objects.
No matter how hard you try, you can’t superimpose a molecule of (+)-lactic acid on a molecule
of (-)-lactic acid. If any two groups match up, the remaining two groups don’t match
Chiral centre
• Chiral centre: A tetrahedral atom, most commonly carbon, that is bonded to four different
groups.
• A carbon atom with four different groups bonded to it lacks the two key symmetry elements
and is called a chiral centre.
• other terms for chiral center: stereocenter, asymmetric center, and stereogenic center
Optical isomerism:
• When a beam of ordinary light passes through a device called a polarizer, only the light
waves oscillating in a single plane pass through and the light is said to be plane-polarized
light. Light waves in all other planes are blocked out.
• when a beam of plane-polarized light passes through a solution of certain organic molecules,
such as sugar or camphor, the plane of polarization is rotated through a certain angle.
• Not all organic substances exhibit this property.
• Substances those rotate a plane of polarized light are called optically active.
• some optically active molecules rotate polarized light to the left (counterclockwise) and are
said to be levorotatory, whereas others rotate polarized light to the right (clockwise) and are
said to be dextrorotatory.
• By convention, rotation to the left is given a minus sign (─) and rotation to the right is given
a plus sign (+).
• The extent of rotation observed in a polarimetry experiment depends on the number of
optically active molecules encountered by the light beam. This number depends on sample
concentration and sample pathlength.
• If the concentration of the sample is doubled, the observed rotation doubles.
• If the concentration is kept constant but the length of the sample tube is doubled, the
observed rotation doubles.
• It also depends on the wavelength of the light used.
• The specific rotation, [α]D, of a compound is defined as the observed rotation when light of
589.6 nm wavelength is used with a sample pathlength of 1 dm and a sample concentration
of 1 g/cm3. (Light of 589.6 nm, the so-called sodium D line, is the yellow light emitted from
common sodium street lamps.)
Two enantiomers rotate plane polarized light to exactly the same extent but in opposite
directions.
Racemic mixture:
• Racemic mixture: An equimolar mixture (equal amounts) of two enantiomers.
• Because a racemic mixture contains equal numbers of dextrorotatory and levorotatory
molecules, its specific rotation is zero. It is represented as (±) or (d, l).
RS Configuration:
Rules: (Cahn-Inghold-Prelog System)
• Look at the four atoms directly attached to the chirality center, and rank them according to
atomic number.
• If a decision can’t be reached by ranking the first atoms in the substituent, look at the second,
third, or fourth atoms away from the chirality center until the first difference is found.
• Multiple-bonded atoms are equivalent to the same number of single-bonded atoms.
• Arrange the molecule in space so that the group of lowest priority (4) is directed away from
you, analogously to the steering column of a car. The three groups of higher priority (1–3)
then project toward you
• Read (or draw curved arrow) the three groups
projecting toward you in order from highest
priority (1) to lowest priority (3). If the groups are
read in a clockwise direction, the configuration is
designated as R (Latin: rectus, straight, correct); if
they are read in a counter-clockwise direction, the
configuration is S (Latin: sinister, left)
(S)-Glyceraldehyde (R)-Glyceraldehyde
Exercise
Diastereomers
• Diastereomers are stereoisomers that are not mirror images.
• To be diastereomers, need at least 2-chiral centres
• The relationship between diastereomers is like that of hands from different people. Your hand
and your friend’s hand look similar, but they are not identical and they are not mirror images
• (a) and (c) are diastereomers. (b) and (d) are diastereomers
• (a) and (d) are diastereomers. (b) and (c) are diastereomers
Epimers: Special case where two diastereomers differ at only one
chirality center but are the same at all others, we say that the
compounds are epimers
Meso compounds
• Compounds that are achiral, but contain chirality centres, are called meso compounds.
• Possible when more than one chiral centres are present.
The four stereoisomers of tartaric acid can be drawn as follows:
A close look at the 2R,3S and 2S,3R structures shows that they are superimposable, and thus,
identical, as can be seen by rotating one structure 180°. The molecule has a plane of symmetry
and is therefore achiral.
Thus, tartaric acid
exists in three
stereoisomeric forms:
two enantiomers and
one meso form.
Exercise
Types of Organic Reactions
Addition reactions:
Elimination reactions:
Substitution reactions:
Rearrangement reactions:
Bond-breaking and bond-making in organic reactions:
Homolytic cleavage:
Heterolytic cleavage:
Symmetrical bond-making:
Unsymmetrical bond-making:
Nucleophiles and Electrophiles:
Nucleophiles:
• Substance that is “nucleus-loving.” (nucleus is positively charged.)
• Negatively polarized, electron-rich atom and can form a bond by donating a pair of electrons
to an electrophile.
• Either neutral or negatively charged
Electrophiles:
• An electrophile is “electron-loving.”
• positively polarized, electron poor atom and can form a bond by accepting a pair of electrons
from a nucleophile.
• either neutral or positively charged
Exercise
Electron Movement in Organic Reactions:
Movement of electron pair:
Movement of single electron:
Electron Displacement Effects in Covalent Bonds :
Inductive effect:
• Permanent effect
• Inductive effect is the shifting of electrons in a σ-bond in response to the electronegativity of
nearby atoms.
• Metals, such as lithium and magnesium, inductively donate electrons.
• Reactive nonmetals, such as oxygen and nitrogen, inductively withdraw electrons.
• Electron withdrawing groups (─I) : ─X, ─NO2, ─CN, ─COOH, ─COOR, ─OAr
• Electron releasing groups (+I) : ─CH3, ─CH2CH3, ─NH2
Resonance effect OR Metameric effect:
• Permanent effect
• Resonance effect is the withdrawal or donation of electrons through a pi bond due to the
overlap of a p orbital on the substituent with a p orbital on the aromatic ring.
• Electron withdrawing groups (─R or ─M) : ─COOH, ─CHO, ─CO, ─CN, ─ NO 2
• Electron releasing groups (+I or +M) : ─CH3, ─CH2CH3, ─NH2, ─OR, ─OCOR, ─NHCOR, ─NHR
• Inductive effects and resonance effects don’t necessarily act in the same direction.
• -X, -OH, -OR, and –NH2 have electron-withdrawing inductive effects because of the
electronegativity of the -X, -O, or -N atom bonded to the aromatic ring but have electron-
donating resonance effects because of the lone-pair electrons on those -X, -O, or -N atoms.
• When the two effects act in opposite directions, the stronger one dominates.
• Thus, -OH, -OR, and –NH2 are activators because their stronger electron-donating resonance
effect outweighs their weaker electron-withdrawing inductive effect.
• Halogens are deactivators because their stronger electron-withdrawing inductive effect
outweighs their weaker electron-donating resonance effect.
Electromeric effect:
• Temporary effect
• The organic compounds having a multiple bond (a double or triple bond) show this effect in
the presence of an attacking reagent only.
• It is defined as the complete transfer of a shared pair of π-electrons to one of the atoms
joined by a multiple bond on the demand of an attacking reagent.
• The effect disappears as soon as the attacking reagent is removed from the domain of the
reaction.
• Positive electrometric effect:
• Negative electrometric effect:
Hyperconjugation:
• Hyperconjugation involves partial overlapping of the σ-bonding orbital of an adjacent C-H or
C-C bond of the alkyl group with the vacant 2p orbital of the cationic carbon
• The net result of hyperconjugation is an increase of electron density on the cationic carbon,
thereby delocalizing the positive charge onto the adjacent alkyl groups.
• More alkyl groups bonded to a cationic carbon (or more C-H bond to adjacent carbon), the
more effect of Hyperconjugation.
