ISOMERS – compounds having the same molecular formula

but different properties.

ISOMERISM Relates the existence of isomers

ISOMERISM

STRUCTURAL ISOMERISM

STEREOISOMERISM

CHAIN ISOMERISM

• Difference in the arrangement of carbon chain

POSITION

• Differ in the position of groups

FUNCTIONAL

• Presence of different functional groups

METAMERISM

• Differ in the no. of C atoms on either side of functional groups.

RING –CHAIN

• Isomers have open chain and ring structure

TAUTOMERISM

• Isomers exist in dynamic equilibrium

Difference in the arrangement of atoms within molecules having same molecular formula.

STEREOISOMERISM

CONFIGURATIONAL

GEOMETRICAL

OPTICAL

CONFORMATIONAL

Isomers that differ in the way the atoms are oriented in space, but not in which atoms are bonded to which other atoms i.e. have same molecular and structural formula but different spatial arrangement

non-polarized polarized

OPTICAL ACTIVITY

• Property of a substance to rotate the plane of plane polarized light.

PLANE POLARIZED LIGHT

• light that has been passed through a nicol prism or other polarizing medium so that all of the vibrations are in the same plane

OPTICAL ISOMERISM Isomers have same properties but differ only in their effect on polarised light

FUNDAMENTAL TERMS

POLARIMETER – an instrument used to measure optical activity.

light source sample tube

polarizer analyzer

OPTICAL ACTIVITY

Plane-polarized light when passes through solutions of

achiral compounds remains in the same plane

Solutions of chiral compounds rotate plane-polarized light

and the molecules are said to be optically active

Phenomenon discovered by Biot in the early 19th century

DEXTROROTATORY – when the plane of polarized light is rotated in a clockwise direction when viewed through a polarimeter.

(+) or (d)

LEVOROTATORY – when the plane of polarized light is rotated in a counter-clockwise direction when viewed through a polarimeter.

(-) or (l)

The angle of rotation of plane polarized light by an optically active substance is proportional to the number of atoms in the path of the light.

SPECIFIC ROTATION – the angle of rotation of plane polarized light by a 1.00 gram per cm-3 sample in a 1 dm tube. [α ]D (D = sodium lamp, λ = 589 mμ).

α [ α ]D = where α = observed rotation l * d l = length (dm) d = concentration (g/cc) (+)-alanine [ α ]D = +8.5 (-)-lactic acid [α ]D = -3.8

• PLANE OF SYMMETRY – A plane which divides a molecule into two halves that are exact

mirror images

• STEREOGENIC /CHIRAL CENTRE – A carbon atom bonded to 4 different atoms or groups.

• CHIRAL – Molecules that are not superimposable on their mirror images are

chiral .

• ACHIRAL – A molecule with a plane of symmetry is the same as its mirror image

and is said to be achiral .

• CHIRALITY OR HANDEDNESS – The lack of a plane of symmerty in a molecule

TERMS

- Compounds with one chiral center show optical activity

- Some compounds without chiral centers also show optical acitivity e.g. allenes and substituted biphenyls

- Compounds with more than one chiral center may or may not show optical activity depending on whether they are non-superimposable on their mirror image (chiral) or superimposable (achiral).

OPTICAL ACTIVITY

ENANTIOMERISM

Louis Pasteur (1848) recrystallized sodium ammonium tartrate

(optically inactive). He noticed that the crystals were of two

types which he physically separated. The two types of crystals

were optically active, but rotated the plane of polarized light in

opposite directions. He proposed that the molecules came in

two forms, “left handed” and “right handed”. Together, the

mixture of the two forms is optically inactive.

DISCOVERY OF ENANTIOMERS

ENANTIOMERS – Non superimposable mirror-image stereoisomers.

Same physical properties except the direction of rotation of the plane of a plane polarized light

Same chemical properties except the reaction with optically active reagents.

Different biological properties

Mixture of equal quantities of enantiomers give an optically inactive form called racemic mixture ( ± )

CHARACTERISTICS OF ENANTIOMERS

EXAMPLES OF ENANTIOMERS

• Molecules that have one carbon with 4 different substituents have a nonsuperimposable mirror image – enantiomer

MIRROR-IMAGE FORMS OF LACTIC ACID

• When H and OH

substituents match up,

COOH and CH3 don’t

• when COOH and CH3

coincide, H and OH don’t

CONFIGURATION – the arrangement in space of the four different groups about a chiral center.

REPRESENTATION OF CONFIGURATIONS

“wedge” formulas Fischer projections “cross structures” use only for chiral centers!

Br

F

HCl

Br

F ClH

In the Fischer projection, the horizontal bonds to the chiral center are always above the plane and the vertical bonds to the chiral center are below the plane. (the horizontals are “hugging you.”

CH3

H

Br Cl

CH3

H

ClBr

DIASTEREOMERS

• Molecules with more than one chiral center have

non-superimposable mirror image stereoisomers called

enantiomers

• In addition they can have stereoisomeric forms that are not

mirror images, called diastereomers

THREONINE

2R,3R 2S,3S 2R,3S 2S,3R

Relationships Among Four Stereoisomers of Threonine

CHARCTERISTICS OF DIASTEREOMERS

They have different physical properties .

Can be separated easily by fractional distillation,

crystalisation etc.

May have optical rotation in the same or opposite

directions but to a different extent.

Have identical chemical properties but differ in rate of

reactions with optically active compounds

MESO COMPOUNDS

An achiral compound with more than one chiral centers is called a meso compound – it has a plane of symmetry

Eg: Tartaric acid has two chirality centers and two diastereomeric forms

One form is chiral and the other is achiral, but both have two chirality centers

An Achiral compound III / IV are meso compounds.

I CHIRAL II III ACHIRAL IV

TARTARIC ACID

Enantiomers What are they?

MESO COMPOUND

RACEMIC MIXTURES AND THE RESOLUTION OF ENANTIOMERS

• A 50:50 mixture of two chiral compounds that are mirror images does not rotate light – called a racemic mixture (named for “racemic acid” that was the double salt of (+) and (-) tartaric acid

• The pure compounds need to be separated or resolved from the mixture (called a racemate)

• To separate components of a racemate (reversibly) we make a derivative of each with a chiral substance that is free of its enantiomer (resolving agent)

• This gives diastereomers that are separated by their differing solubility

• The resolving agent is then removed

Using an Achiral amine doesn’t change the relationship of the products Still can’t separate the Enantiomeric Salts

Using a Chiral amine changes the relationship of the products Now we can separate the Diastereomeric Salts

• The original method was a correlation system, classifying related molecules into “families” based on carbohydrates – Correlate to D- and L-

glyceraldehyde

– D-erythrose is the mirror image of L-erythrose

• This does not apply in general

SPECIFICATION OF CONFIGURATION :D AND L SYSTEM

CAHN, INGOLD, PRELOG SEQUENCE RULES:

Rule 1:

• Look at the atoms directly attached to the chiral carbon and assign priority based on highest atomic number (O > N > C > H)

Rule 2:

• If decision can’t be reached by ranking the first atoms in the substituents, look at the second, third, or fourth atoms until difference is found

Rule 3:

• Multiple-bonded atoms are equivalent to the same number of single-bonded atoms

SPECIFICATION OF CONFIGURATION: THE R/S. SYSTEM

Br

F

Cl H

1

2

3

4

OH

CH2Br

CH3H

1

2

34

CH2CH3

H

CH=CH2Br1 2

3

4

R/S:

1. Using the Cahn, Ingold, Prelog sequence rules, assign

numbers to each of the four groups attached to the chiral

center.

2. Rotate the number 4 group away from you and observe

the sequence 1 2 3 for the remaining groups.

3. If going from 1 2 3 is clockwise, then the

configuration is R (rectus). If the sequence 1 2 3

is counter-clockwise, then the configuration is S

(sinister).

21

3

12

3

R S

With group #4 rotated away:

Cl

Br

H F

1

2

34Cl

Br

F

1

2

3

rotate #4 away

(S)-configuration

S S

EXAMPLES

GEOMETRICAL ISOMERISM

Compounds having double bonds (C=C, C=N, or N=N) and alicyclic compounds exhibit geometrical isomerism.

Hindered rotation around double bond; and single bonds in rings is the cause for isomerism.

Isomers can’t be interconverted without breaking or making of bonds.

Also known as Cis-Trans isomerism.

GEOMETRIC ISOMERISM

C C

CH3

H

H

CH3

Cannot rotate around C=C

X

GEOMETRICAL ISOMERISM BY ALKENES

Alkenes in which each of the two carbon atoms of the double bond have different groups show isomerism.e.g. abC= C ab and abC=Cde

Alkenes having same groups or atoms attached to one or both the doubly bonded carbon atoms do not show isomerism.e.g. aaC = Ced and aaC=Cbb.

CIS ISOMERS • The same groups are on the same side of the C=C bond

C C

CH3

H

CH3

H

cis but-2-ene

TRANS ISOMERS • Same groups are on

opposite sides of the C=C bond

C C

CH3

H

H

CH3

trans but-2-ene

GEOMETRIC ISOMERISM

Z 2-bromo-2-fluorobut-2-ene

E-Z nomenclature is based upon the sequence rules developed by Cahn Prelog and Ingold PRIORITY: H < CH3 < CH2CH3

Highest priority groups on opposite side = E

Highest priority groups on same side = Z

F

C C

CH3

BrCH3

12

35

9

12

H

C C

CH2CH3

CH3CH3

12, 12

12

1

12

E 3-methylpent-2-ene

GEOMETRIC ISOMERISM

C C

CH3

H

H

CH3

C C

CH3

H

CH3

H

(E) but-2-ene (Z) but-2-ene

E entgegen (opposite) Z zusammen (together)

H H

C=C

H CH2CH3

Geometric isomerism does not

exist because one C has two

identical atoms attached

But-1-ene

GEOMETRICAL ISOMERISM WITH MORE THAN ONE DOUBLE BOND

• Structures with n different double bonds exist in 2n geometrically isomeric forms

• Example where n=2 is shown as

Fig: geometrical isomerism in a diene

Note: these are also configurational diastereomers

Substituents on same side or opposite side of two carbons which may or may not adjacent in the ring

CIS-TRANS ISOMERISM IN RINGS

PROPERTIES OF GEOMETRIC ISOMERS

• Geometric isomers have similar chemical properties.

• Geometric isomers have some different physical

properties.

• DIPOLE MOMENTS OF:

Whereas the moments of the corresponding trans isomer are zero

EXAMPLE

DIFFERENT COMPOUNDS- DIFFERENT M.P. AND DENSITY

EXAMPLE

Difference in heat of hydrogenation of cis & trans stilbene = 5.7 kcal/mole

Stability of the cis- stilbene is less as compared to the trans isomer

CONFIGURATION OF OXIMES

o Configuration of Oximes identified by prefixes “syn” & “anti”

instead of cis & trans

o In Aldoxime the syn isomer- in which –OH group of the oxime

is on the side of the hydrogen of the aldehyde carbon

o In Ketoxime – specify the group with respect to which the

oxime –OH group is syn

GEOMETRICAL ISOMERS DUE TO C=N AND N=N

CLASSIFICATION

CONFORMATIONAL ISOMERISM

• Different spatial arrangements due to rotations of

groups or atoms about a single bond are called

conformations.

• Conformations are readily interconvertible just by

rotation around a single bond

• Doesn’t require breaking or making of bond

• Conformations exists only as mixture of isomers.

“staggered” “eclipsed”

torsional strain: deviation from staggered.

Newman projections:

H

H H

H

HH

H

H H

H

H H

H

HH

H

H

H H

H

HH

H

H

DEFINITIONS

• Staggered - A low energy conformation where the bonds on adjacent atoms bisect each other (60o dihedral angle), maximizing the separation.

• Eclipsed - A high energy conformation where the bonds on adjacent atoms are aligned with each other (0o dihedral angle).

DEFINITIONS • Anti - Description given to two substitutents attached

to adjacent atoms when their bonds are at 180o with respect to each other.

• Syn - Description given to two substitutents attached to adjacent atoms when their bonds are at 0o with respect to each other.

• Gauche - Description given to two substitutents attached to adjacent atoms when their bonds are at 60o with respect to each other.

TYPES OF STRAIN

• Steric - Destabilization due to the repulsion between the electron clouds of atoms or groups. Groups try to occupy some common space.

• Torsional - Destabilization due to the repulsion between pairs of bonds caused by the electrostatic repulsion of the electrons in the bonds. Groups are eclipsed.

• Angle - Destabilisation due to distortion of a bond angle from it's optimum value caused by the electrostatic repulsion of the electrons in the bonds. e.g. cyclopropane

CONFORMATIONS OF ETHANE

NEW MANS PROJECTIONS FORMULAE

• eclipsed conformation

Ethane

Ethane

• eclipsed conformation

Ethane

• staggered conformation

Ethane

• staggered conformation

The Newman Projection

Projection Formulas of the Staggered Conformation of Ethane

Newman Sawhorse

H

H

H H

H H

H

H H H

H

H

CONFORMATIONAL ANALYSIS OF ETHANE

A conformational analysis is a study of the energetics of different spatial arrangements of atoms relative to rotations about carbon-carbon single bonds.

Rotational Conformations of Ethane

60o ROTATION CAUSES TORSIONAL OR ECLIPSING STRAIN

Potential Energy Diagram

rotation about C-C

pote

ntial energ

y

3 Kcal

The barrier to rotation about the carbon-carbon bond in ethane is 3 Kcal/mole. The rotation is ~ “free.”

•The eclipsed conformation of ethane is 12 kJ/mol less stable than the staggered.

•The eclipsed conformation is destabilized by torsional strain.

•Torsional strain is the destabilization that results from eclipsed bonds.

TORSIONAL STRAIN

CONFORMATIONAL ANALYSIS OF PROPANE

Propane Conformations: Larger Barrier to Rotation

staggered eclipsed

H

HH

H

H

CH3 CH3

H

HH

H

H

rotation about C-C

pote

ntial energ

y

3.4 Kcal

CONFORMATIONAL ANALYSIS OF BUTANE

In butane, two of the substituents, one on each carbon atom being viewed, is a methyl group. Methyl groups are much larger than hydrogen atoms

Butane Conformations (C2-C3)

CONFORMATIONAL ANALYSIS OF n-BUTANE

Gauche Interaction in Butane

2 Different Eclipsed Conformations

Strain Energy can be Quantified

Butane has Steric and Torsional Strain When Eclipsed

PE Diagram for Butane

H

H

H H

H H

H

H H H

H

H 180°

Anti Relationships

•Two bonds are anti when the angle between them is 180°.

H

H

H H

H H

H

H H H

H

H

60°

Gauche Relationships

•Two bonds are gauche when the angle between them is 60°.

An important point:

•The terms anti and gauche apply only to bonds (or groups) on adjacent carbons, and only to staggered conformations.

CH3

CH3H3C

CH3

H3C

CH3

H3CCH3

anti

gauche

3.4 Kcal

4.4-6.1 Kcal

0.8 Kcal

pote

ntial e

nerg

y

rotation

conformations about C2-C3 in n-butane:

0° 60° 120° 180° 240° 300° 360°

12 kJ/mol

CONFORMATIONS OF CYCLOHEXANE

• Cyclohexane is a multiplanar compound having sp3 hybrid carbons

• Bond angles are equal to tetraheral angle

• Two important conformations

– Chair

– Boat

Cyclohexane

Chair Conformation

Boat Conformation

Rings can Flip from one Chair Conformation to Another

Flipping Chair Conformations

• All axial bonds become equatorial

• All equatorial bonds become axial

• All “up” bonds stay up

• All “down” bonds stay down

Axial-up becomes Equatorial-up

Equatorial Conformation is Preferred

Axial Methyl group is Gauche to C3 in the ring

Gauche Interactions are Flagged by Parallel H’s

1,3-Diaxial Interactions

Equatorial Methyl Group is Anti to C3 in the ring

All of the bonds are staggered and the bond angles at carbon are close to tetrahedral.

CHAIR IS THE MOST STABLE CONFORMATION OF CYCLOHEXANE

All of the bond angles are close to tetrahedral but close contact between flagpole hydrogens

causes van der Waals strain in boat.

180 pm

BOAT CONFORMATION IS LESS STABLE THAN THE CHAIR

Eclipsed bonds bonds gives torsional strain to boat.

BOAT CONFORMATION IS LESS STABLE THAN THE CHAIR

Less van der Waals strain and less torsional strain in skew boat.

Boat Skew boat

SKEW BOAT IS SLIGHTLY MORE STABLE THAN BOAT

Half-

chair

Skew

boat

45 kJ/mol 45 kJ/mol

23 kJ/mol

•the chair conformation of cyclohexane is the most stable conformation and derivatives of cyclohexane almost always exist in the chair conformation

GENERALIZATION

3.8 Axial and Equatorial

Bonds in Cyclohexane

Axial bonds and Equatorial bonds

The 12 bonds to the ring can be divided into two

sets of 6.

Axial bonds point "north and south"

6 Bonds are axial

Equatorial bonds lie along the equator

6 Bonds are equatorial

a a

aa

a

a

e

ee

ee

e

a = axial positions in the chair conformation

e = equatorial positions

CH3

H3C

CH3 in axial position CH3 in equatorial position

is more stable

CONFORMATIONAL INVERSION (RING-FLIPPING) IN

CYCLOHEXANE

•chair-chair interconversion (ring-flipping)

•rapid process (activation energy = 45 kJ/mol)

•all axial bonds become equatorial and vice versa

CONFORMATIONAL INVERSION

• Most stable conformation is chair

• Substituent is more stable when equatorial

CONFORMATIONAL ANALYSIS OF MONOSUBSTITUTED CYCLOHEXANES

5% 95%

•Chair chair interconversion occurs, but at any instant 95% of the molecules have their methyl group equatorial.

•Axial methyl group is more crowded than an equatorial one.

METHYLCYCLOHEXANE

CH3

CH3

5% 95%

•Source of crowding is close approach to axial hydrogens on same side of ring.

•Crowding is called a "1,3-diaxial repulsion" and is a type of van der Waals strain.

METHYLCYCLOHEXANE

END