STEREOCHEMISTRY

STEREOCHEMISTRY OF
SOME ORGANIC
COMPOUNDS
DEFINITION OF
STEREOCHEMISTRY
• Greek term stereos = solid.
• Science of organic chemistry.
• Deals with structure in three
dimensions.
• Based on the relationship between
molecular structure and properties.

Contd.
• Study of the static and dynamic aspects of the three
dimensional shape of molecules.
• Provides foundation for understanding structure and
mechanism in organic chemistry.
 ABOUT ORGANIC COMPOUNDS
Organic Compounds

Hydrocarbons
(H & C elements)

Aliphatic Aromatic

Alkanes Alkenes Alkynes Cyclic

aliphatic
H H Benzene
H
C C H C C H
H C H H H
Acetylene
H Ethene
Methane
Cyclohexane
 HISTORY
• Beginning of Organic Stereochemistry
 French Physicist Jean-Baptiste Biot
(1815)
 Found certain organic compounds /
molecules rotate the plane of the polarized
light in solution or in gas.
 This activity is called as Optical Activity.

Contd.
• Louis Pasteur (1848)
 Describe optical activity is due to the
presence of some dissymmetric grouping
of atoms in a molecule.
 Experiments made on tartaric acid.
 Confirmed asymmetric grouping (Chiral
carbon atom) is required for optical
activity.
• Jacobus H. van’t Hoff and J.A. LeBel (1874)
 Laid foundation of stereochemistry
 Postulated asymmetric carbon model
(tetrahedral arrangement)

Contd.
 Concept of three dimensional structure
 Chemistry Nobel Prize 1901 (First
recipient of prize)
 Shape and size of Tetrahedral carbon
atom in methane
 Proposal of tetrahedral carbon base on
 Evidence of Isomer number (Greek:
isos = identical, meros = part)
 Only the tetrahedral structure
for methane agrees with the evidence
of isomer number.
Contd.
 Tetrahedral carbon shape and size
out of plane of paper (front)
behind plane of paper (back)
in plane of paper
C H Bond length 1.10 Ao
(1.25 cm = 1.00 Ao)
CHIRAL CARBON ATOM
• Greek word cheir = hand
• A chiral object is not superimposable on its
mirror image.
• Any object that cannot be superimposed on its
mirror image is said to chiral i.e. it possesses the
property of ‘handedness’ (our left hand is the
mirror image of our right hand but the two hands
are not superimposable) [to superimpose the two
hands plane has to be changed].
• Chiral objects – hand gloves, shoes.
CHIRALITY/ASYMMETRY
• Chirality or asymmetry
• Chirality = handedness/phenomenon shown by chiral
carbon atom.

O OH HO O
C C

H C* OH HO C* H

CH3 CH3
Lactic acid
out of plane of paper (front)
behind plane of paper (back)
* Chiral carbon atom
CHIRALITY/ASYMMETRY
COOH COOH
H C OH HO C H
CH3 CH3

Lactic acid
• Molecules that are not superimposable on their
mirror images are chiral.
• A carbon atom to which four different groups are
attached is called chiral center/chiral carbon.
ISOMERS
• Greek word isos = identical, meros = part
• Isomers are different compounds that have the same
molecular formula.
• Isomers are non-identical molecules with the same atomic
composition.
 Isomers

Constitutional isomers Stereoisomers

Different functional group

Stuructural isomers Positional isomers
isomers

O H
CH3 CH3 CH3
CH3
C OH C O
CH2 H3 C CH

CH2 CH3
Br
OH
CH3 2-Methylpropane Br
(C4 H10 ) 2-Bromotoluene o-Hydroxybenzaldehyde
3-Bromotoluene Benzoic acid
n-Butane (C7 H7 Br) (C7 H6 O2 )
(C7 H7 Br) (C7 H6 O2 )
(C4 H10 )
ISOMERISM
• ism suffix forming nouns – an action or its results
• The phenomenon whereby a single molecular formula can
represent more than one compound is called isomerism.

O H H O
C C
H C OH HO C H
IsomersCHofOHGlyceraldehydeCH(C
2
3H6O3)
OH
2
STEREOISOMERS
• Isomers studied with three dimensional aspects are called
as stereoisomers.

STEREOISOMERISM
• The phenomenon whereby a single molecular formula can
represent more than one compound in three dimensions is
called stereoisomerism.
STEREOISOMERISM
• Stereoisomerism occurs in molecules with identical
structures, by which is meant they have the same order of
atoms but differ in their spatial arrangement
(configuration) in relation with chiral carbon atom.
 CLASSIFICATION OF STEREOISOMERS
Stereoisomers

Configurational Conformational
stereoisomers stereoisomers

Enantiomers Diastereomers Geometric isomers Relative isomers Absolute configuration

(mirror images) (not mirror images)

(non superimposable)

Optical isomers Meso structures cis trans Z E R S

Erythro Threo D L

Dextro Levo Racemic

(d) (+) (l )(-) (dl) (±)
 CONFIGURATION
• Configuration - manner of arrangement/ shape/outline.
• Arrangement of atoms that characterises a particular
stereoisomer is called configuration.
• Probability.
CONFIGURATIONAL
STEREOISOMERS
• Configurational stereoisomers – manner of
arrangement/shape/outline/attachment of atoms in
three dimensions.
• Configurational stereoisomers, interconverted by
inversion (turning-inside-out) at a chiral center.
ENANTIOMERS
• Enantiomers Greek word enantio = opposite
• Isomers that are mirror image of each other are called
enantiomers.
• Two stereoisomers that are not superimposable
mirror image of each other.

CH3 CH3

H C Cl Cl C H

Cl C H H C Cl

C 2H 5 C 2H 5

2,3-Dichloropentane
 Cl H H Cl

H Cl Cl H
1,2-Dichlorocyclopentane
• Enantiomers have identical chemical properties except
towards optically active reagents.
• Have identical physical properties, except for the ‘chiral’
direction of rotation of the plane of polarised light.
ENANTIOMERISM
• The phenomenon of formation of enantiomers is called
enantiomerism.
OPTICAL ISOMERS
• Optical visual; of or according to optics.
• Optic of eye or sight.
• Some substances rotates the plane of polarization and such
substances are called optically active.
• If the rotation of plane is to the right (clockwise) the
substance is dextrorotatory (Latin: dexter = right) denoted
by (d) or (+).
• If the rotation of plane is to be left (counter clockwise) the
substance is levorotatory (Latin: laevus = left) denoted by
(l) or (-).
OPTICAL ISOMERS
• The two forms are called optical isomers.
• Mirror image non superimposable.
• Optical isomers also called enantiomers.
O OH HO O
C C
H C OH HO C H
CH3 CH3

(d) or (+) Lactic acid (l) or (-) Lactic acid

• The phenomenon is called optical isomerism.
 OPTICAL ISOMERS
O H H O
C C
H C OH HO C H
CH2OH CH2OH

(d) or (+) Glyceraldehyde (l) or (-) Glyceraldehyde

RACEMIC MODIFICATION
• A mixture of enantiomers is called a racemic
modification.
• Racemic modification is optically inactive if the
mixture is 50:50.
• When enantiomers are mixed together, the rotation
caused by a molecule of one isomer is exactly
cancelled by an equal and opposite rotation caused
by a molecule of its enantiomer.
• (dl) or (±) – lactic acid.
DIASTEREOMERS
• Dia means two.
• For more than one chiral centers.
• Stereoisomers that are not mirror images of each others
are called diastereomers.
• Diastereomers are stereoisomers but not enantiomers.
DIASTEREOMERS
CH3 CH3

H C
*
Cl H C* Cl

Cl C* H H C* Cl

C 2H 5 C2H5
2,3-Dichloropentane
(not mirror image)

* chiral carbon atom

 DIASTEREOMERS
• Diastereomers have different physical properties.
• Chemical properties are not identical.
• May be optically inactive.
• The phenomenon of formation of diastereomers is called
diastereoisomerism.
MESO STRUCTURES
• Molecules have symmetric end – the term Meso is used.
• Meso means combining form middle, intermediate.
• A Meso compound is one whose molecules are
supeimposable on their mirror images even though they
contain chiral centers.
• A Meso compound is optically inactive.
MESO STRUCTURES
CH3 CH3

H C Cl Cl C H

H C Cl Cl C H

CH3 CH3

2,3-Dichlorobutane

• Superimposable; turned end-for-end a Meso compound

(in same plane).
 MESO STRUCTURES
• In meso structure one half of the molecule is the mirror
image of the other half.
CH3
H C Cl
H C Cl
CH3

2,3-Dicholorobutane
• In meso compounds two chiral centers have opposite
configuration.
GEOMETRIC ISOMERS
• Science of properties and relations of lines (bond).
• Not require chiral carbon atom.
• The particular kind of diastereomers that owe their
existence to hindered rotation about double bonds are
called geometric isomers.
GEOMETRIC ISOMERS
• The configurations of the isomeric 2-
butenes

H CH3 H3C H
C C
C C
H CH3 H CH3

cis-2-Butene trans-2-Butene
(not mirror image)
• cis – (Latin: on this side or same side or identical
groups)
• trans – (Latin: across or opposite)
GEOMETRIC ISOMERISM
• The phenomenon of forming geometric isomers is called
geometric isomerism.
• A pair of geometric isomers, are, then diastereomers, as
they are not mirror images.
• Geometric isomers, interconverted – in principle – by
rotation about a double bond.
• Geometric isomers have different physical and frequently
different chemical reactivities.
GEOMETRIC ISOMERS CYCLIC
COMPOUNDS
H
H

cis-Decalin
H cis-Decalin
H

H H
trans-Decalin trans-Decalin
GEOMETRIC ISOMERS
Z AND E
• Z German : Zusammen = together, same side
• E German : entgegen = opposite, opposite side

H3C H H3C H Priority

C C
C C
CH3 > H
(Z)-1-Bromo-
Br Cl (E)-1-Bromo-
Cl Br
Br > Cl
1-chloropropene 1-chloropropene
RELATIVE
CONFIGURATION
Erythro and Threo isomers
• Used for molecules having non-symmetric ends.
• Generally used in Fischer projection.
• Not mirror images.
• Resembles with diastereomers.
Erythro and Threo isomers
• Two like functional groups

Same side Opposite side

(Erythro) (Threo)

O H H O

H OH HO H
H OH H OH
CH2OH CH2OH
Erythrose Threose
RELATIVE
CONFIGURATION
D and L isomers
• Used for molecules having non symmetric
ends.
• Orientation of –H and –OH on chiral carbon
which is farther most from the primary
chiral carbon.
• Generally used in Fischer projection.
D and L isomers
H O H O

H OH H OH
HO H HO H
H OH H OH
H OH D L HO H
CH2OH CH2OH

D-Glucose L-Glucose
ABSOLUTE CONFIGURATION
R and S isomers
• Suggested by Cahn, Ingold and Prelog (CIP).
• R Latin : rectus = right
• S Latin : sinister = left
R.S. Cahn (The Chemical Society, London)
Sir Christopher Ingold (University College, London)
R and S isomers
• V. Prelog (Eidgenossiche Technische Hochschule, Zurich)
• CIP system most frequently used for designating absolute
configurations of chiral compounds.
R and S isomers
• Sequence rules
1) Arrange the ligands associated with an element of chirality
into order of priority.
Priority Rules
• Higher atomic number is given higher priority.
• Higher atomic mass is given higher priority.
R and S isomers
 cis > trans
 [(R, R)] or (S, S)] > [(R, S) or (S, S)].
 I > Br > Cl
2) View the molecule with the lowest priority group pointing
away from the viewer.
3) Count the remaining ligands in order of decreasing
priority.
R and S isomers
• If the path traced is clockwise, the (R) absolute
configuration is assigned.
• If the path traced is counterclockwise, the (S)
absolute configuration is assigned.

Br Br
Priority
I C Cl Cl C I
I > Br > Cl > H
H H

R S
Bromochloroiodomethane
R and S isomers

Br Br
Priority
H H
I > Br > Cl > H
I Cl Cl I
R S

Atoms
I > Br > Cl > H
priority
At. No. 53 35 17 1
At. Wt. 126.91 79.91 35.06 1.008
R and S isomers

CH2CH3 CH2CH3
HO H H OH
CH3 CH3

(-)-2-Butanol (+)-2-Butanol
Relative configuration

CH2CH3 CH2CH3
H H Priority
HO > CH3CH2 > CH3
HO CH3 H3C OH
(R)-2-Butanol (S)-2-Butanol
Absolute configuration
Forms of representing organic compounds

Cyclic
Noncyclic
compounds
compounds

Ethane

Empirical Molecular Structural

formula formula formula

CH3
C2H6
(C:H; 1:3) Contd.
 Ethane Structural
formula

Chain formula H3C CH3

H H Newman
(normal chain) H H projection
H

H H HH
Electronic
Fischer formula H C CH
H H H H
formula
H

Andiron formula Ball & Stick

(Sawhorse drawing) H
H
H
H formula
H

Dimensional formula H
H

H C
(Wedge-and-dash C H
H
drawing) H
 Cyclic compounds

Cyclohexane

Emperical Molecular Structural

formula formula formula

CH2 C6 H12
Contd.
 Cyclohexane
structural formula

Haworth Wedge-and-
Chain formula
projection dash drawing

H
Polygon H
H
H
formula H
H
H H

H H
H H

Ball and Newman Chair

Stick formula projection formula
 Conformational
Stereoisomers

Eclipsed Chair

Staggered Boat

Skew Twist boat

Anti Half chair

Gauche
 CONFORMATIONS
• Different arrangements of atoms that can be converted into
one another by rotation about single bonds are called
conformations.

H
HH
H
H H
H H
H H
H H

Andiron formula Newman projection

Eclipsed conformation ethane

CONFORMATIONS
H H
H H
H H
H H H H
H
H

Staggered conformation Ethane

• The infinity of intermediate conformations are called

skew conformations.
CONFORMATIONS
CH3
H H

H H
CH3

Anti conformation n-Butane

CONFORMATIONS
CH CH 3 3
H3C H H CH3

H H H H
H H

Gauche conformation n-Butane

• Van der Waals forces
• Repulsive (Steric repulsion)
• Strain (Steric strain)
• Strain (Torsional strain)
• Shielding / Crowding of CH3 groups.
• Mirror images (Conformational) enantiomers
• Anti and Gauche are not mirror images (conformational) diastereomers
CONFORMATIONAL
ISOMERS / CONFORMERS
• Different conformations corresponding to energy
minima are called conformational isomers or
conformers.
• Conformational isomers are interconvertable by
rapid rotations about one or more single bonds (C-
C).
Potential energy changes during rotation about the carbon-carbon single
bond of ethane.
Potential energy changes during rotation about the C(2)-C(3) bond of
n-butane.
Potential energy relationships among conformations of cyclohexane.
CONFORMATIONS OF
CYCLOHEXANE

Chair Boat

Twist-boat Half-chair
CHAIR CONFORMER OF
CYCLOHEXANE
axis

a a
e
e e
a

a
e e
e
a a
CHAIR FORM MOST STABLE
CONFORMATION
• Symmetrical
• Compact
• Completely free of strain-angle/torsional/ Van der
Waals forces (strain/torsion/repulsion).
• Every angle is the tetrahedral angle.
• Every C-C bond precise staggering.
• Energy minima
• No crowding of hydrogen atoms.
 Chair Conformation of
 
Cyclohexane
 
Boat conformation of Cyclohexane
Sawhorse projection formula:
Ethane
 Newman projection formula:
Ethane(Staggered)

Anti conformation; 180 o tortional angle

 Sawhorse &Newman projection
H
formula: Ethane
H
H H
H H H H H H
H H
H H
H
H H H

Staggerd Gauch Conformation Eclipsed

(Most stable) Least stable
180o 60 o
0o
 Conformational Isomerism in Cyclohexane:

Cyclohexane exists in two puckered conformations, the boat and chair

forms, that have tetrahedral bond angles. The boat form is less stable and
not preferred because of interactions between the two end or flagpole
carbons and because the hydrogens on the other adjacent carbons are
eclipsed. In the preferred chair form, atoms on adjacent carbons are
staggered and there are no flagpole type interactions. There are two
orientations of hydrogens in the chair conformation. Axial hydrogens are
oriented directly above or below the "plane" of the ring in an alternating
arrangement. Equatorial hydrogens protrude out along the perimeter of
the ring.
CHAIR FORM MOST STABLE
CONFORMATION
• Everything just fits (geometrical demands).
• Architectural perfection.
• Cyclohexane chairs in the structure of
diamond.
• Diamond most stable form of carbon and the
hardest substance known.
• Replacing one methylene group with
oxygen make up the most abundant building
block of the organic world, D-glucose.
CHAIR FORM MOST STABLE
CONFORMATION

• Appearance of chair form in diamond

CHAIR FORM MOST STABLE
CONFORMATION
D
H
CH
CH22OH
OH
O
HO H

HO H H
OH
H OH 

-D-(+)-Glucopyranose
• Appearance of chair form in
-D-(+)-Glucopyranose
 GLUCOSE NOMENCLATURE

FISCHER PROJECTION
H O O
H

H OH   HO H
HO H HO H
H OH H OH
H OH D H OH D
CH2OH CH2OH
-D-(+)-Glucose -D-(+)-Glucose
FISCHER PROJECTION

O H O
H

H OH   HO H

HO H HO H

H OH H OH

L HO H L HO H

CH2OH CH2OH

-L-(+)-Glucose -L-(+)-Glucose
 HAWORTH CHAIR
PROJECTION CONFORMER
D
CH2OH H
O CH
CH22OH
OH
H H O
H HO H

OH H HO H H
OH OH  OH
H OH 
H OH

-D-(+)-Glucopyranose -D-(+)-Glucopyranose
 HAWORTH CHAIR
PROJECTION CONFORMER
D
CH2OH D
H
O CH2OH
H OH  O
H HO H

OH H HO H OH 
OH H OH
H H
H OH

-D-(+)-Glucopyranose -D-(+)-Glucopyranose
 HAWORTH CHAIR
PROJECTION CONFORMER

H
H
O H
H H O
CH2OH L HO H

OH H HO H
OH OH 
CH2OH OH
H OH 
H OH L

-L-(+)-Glucopyranose -L-(+)-Glucopyranose
 HAWORTH CHAIR
PROJECTION
CONFORMER
H
H
O
H OH  H
O
CH2OH L HO H

OH H HO OH 
OH H
CH2OH OH
H L H
H OH

-L-(+)-Glucopyranose -L-(+)-Glucopyranose
 Ethane
Make a model of ethane, C2H6. Rotate the two carbons relative to each
other around the carbon-carbon bond. Make the staggered and eclipsed
conformations.
Bromoethane
Geometrical isomerism in
oximes
 STEREO
CHEMISTRY OF
SOME DRUG
MOLECULES
 CONFUSING ‘C’
Chemistry

Configurations Carbon Conformations

Compounds

Chirality
THANK YOU