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UNIT –I & II Stereochemistry Isomerism & Geometrical Isomerism BP401T

PHARMACEUTICAL ORGANIC CHEMISTRY –III B. Pharm IV Sem GITAM
(Deemed to be University)
Presentation · December 2018

DOI: 10.13140/RG.2.2.16254.23364
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UNIT –I & II: Stereochemistry Isomerism & Geometrical Isomerism
Stereochemistry Isomerism & Geometrical Isomerism
o Isomerism: Different types of isomerism, their nomenclature and associated physico chemical properties.
o Structural isomerism: chain isomerism, positional isomerism, functional isomerism and metamerism, keto-enol tautomerism.
o Conformational isomerism: Conformations of ethane and butane.
o Geometrical isomerism: Cis-trans isomers and E-Z isomers, physical and chemical properties, stability of cis and trans isomers.
o Optical isomerism: Optical activity, specific rotation, asymmetric carbon, chirality, Fischer projection, enantiomerism,
diastereomerism.
o Specification of configuration: Absolute and relative configuration (D,L system and R,S system). Racemic mixture, racemization.
o Methods of determination of configuration of geometrical isomers.
o Stereo isomerism in biphenyl compounds (Atropisomerism) and conditions for optical activity.
o Stereospecific and stereoselective reactions
 Isomers are compounds that have the same formula but different structures.
 The three main types of isomers are constitutional isomers, conformational isomers and stereoisomers.
 Stereoisomers have the same connectivity but a different spatial orientation. Stereoisomers do not differ from
each other as a result of rotation around single (sigma) bonds. They are different compounds.
 CONNECTIVITY
- The term connectivity means all the atoms in a molecule are connected in the same sequence.
- For a molecule containing atoms A, B, and C; one connectivity is A-B–C while A-C-B is a different connectivity. Both
have the same connectivity but the atoms have a different orientation in space.
- The same atoms or groups are connected to the central carbon atom. The connectivity is the same, but OH and H
are oriented differently in space. To change the positions of H and OH, one would have to break the H-C and HO-C
bonds and connect them in the reverse order.
- The two compounds differ in their connectivity: C–O–C and C–C–O
Dr. Sumanta Mondal _ Lecture Notes _Pharmaceutical Organic Chemistry III– (BP401T)_B.Pharm-IV Sem_GITAM (Deemed to be University) Page | 1
E-mail: logonchemistry@gmail.com
- There are two isomeric compounds with molecular formula C2H6O:

1) Dimethyl ether: a gas at room temperature, does not react with sodium.
2) Ethyl alcohol: a liquid at room temperature does react with sodium.
Properties of ethyl alcohol and dimethyl ether
Properties Ethyl Alcohol (C2H6O) Dimethyl Ether (C2H6O)
Boiling point, °C 78.5 –24.9
Melting point, °C –117.3 –138
Reaction with sodium Displaces hydrogen No reaction
Simple flowchart for classifying various kinds of isomers
 STRUCTURAL ISOMERISM or CONSTITUTIONAL ISOMERS

- Structural isomers are compounds that have same molecular formula but different structural formulas.
- Types of Structural isomers:
(i) Chain isomerism (ii) Position isomerism (iii) Functional isomerism (iv) Metamerism (v) Tautomerism
i. Chain isomerism: It has the same molecular formula but differ in the order in which the carbon atoms are
bonded to each other.
 Number of possible chain-isomers for Alkane

Molecular Formula Possible Number of Constitutional Isomers
C4H10 2
C5H12 3
C6H14 5
C7H16 9
C8H18 18
C9H20 35
C10H22 75
 Physical Constants of the Hexane Isomers
Physical Constants of the Index of

bp (°C)
Hexane Isomers Molecular Structural Formula mp (°C) Refraction
(1 atm)
Formula (nD 20°C)
C6H14 –95 68.7 1.3748
C6H14 –153.7 60.3 1.3714
C6H14 –118 63.3 1.3765
C6H14 –128.8 58 1.3750
C6H14 –98 49.7 1.3688
ii. Position isomerism: It has the same molecular formula but differ in the position of a functional group on the
carbon chain.
iii. Functional isomerism: It has the same molecular formula but different functional groups.
iv. Metamerism: This type of isomerism is due to the unequal distribution of carbon atoms on either side of the
functional group. Member belongs in the same homologous series.
v. Tautomerism: This is special type of functional isomerism in which the isomers are dynamic equilibrium with
each other.
 Tautomerism
- Tautomers are isomers of a compound which differ only in the position of the protons and electrons. The carbon
skeleton of the compound is unchanged. A reaction which involves simple proton transfer in an intramolecular
fashion is called a tautomerism.
- Sometimes the term tautomerism is also called as desmotropism (In Greek desmos-bond; tropos-turn), since the
interconversion of the two forms involves a change of bonds or dynamic isomerism as the two forms are in
dynamic equilibrium with each other.
- Other names for tautomerism are kryptomerism, allelotropism or merotropy; however, tautomerism is the most
widely accepted term.
- There are several types of tautomerism of which keto-enol tautomerism is the most important. In this type, one
form (tautomer) exists as a ketone while the other exists as an enol. The two simplest examples are of acetone
and phenol. The conversion of a keto form into enol from is known as enolisation.
- The most widely studied example of keto-enol tautomerism is that of acetoacetic ester (ethyl acetoacetate).
- Why the KETO form is more stable than ENOL: In most keto-enol tautomerisms, the equilibrium lies by far
toward the keto form, indicating that the keto form is usually much more stable than the enol form, which can be
attributed to the feet that a carbon-oxygen double bond is significantly stronger than a carbon-carbon double
bond.
- Are Tautomers stereoisomers: No, Tautomers are Structural Isomerism or Constitutional Isomers. Tautomers are
two molecules with the same molecular formula but different connectivity - constitutional isomers, in other
words - which can interconvert in a rapid equilibrium. The most common tautomeric relationship in organic
chemistry is the keto-enol pair.
- Types of tautomerism:
1. Prototropic tautomerism
2. Annular tautomerism
3. Non-prototropic tautomerism
4. Ring-chain tautomerism
5. Valence tautomerism
1) Prototropic Tautomerism
- Prototropic tautomerism involves the relocation of an H atom and a double bond.
- One example of prototropic tautomerism is that between keto and enol forms.
- The keto tautomer possesses a C=O group, while the enol form has a vinylic alcohol structure. Increasing acidity
of the α-H affects this tautomerism, favoring-the enol form.
- Conjugated double bonds and intramolecular H-bonds can also stabilize the enol form.
- Other types of prototropic tautomerism are amine-imine tautomerism (e.g. in adenines), amide-imidic acid
tautomerism (related to asparagine-linked glycosylation) and, as a special case, lactam-lactim tautomerism
(present in uracil and thymine).
2) Annular Tautomerism
- This is a special case of prototropic tautomerism, where an H can occupy two or more possible locations in a
heterocyclic system, e.g. imidazole, which can have 1H and 2H tautomers.
1H and 2H tautomers of imidazole
3) Non-Prototropic Tautomerism
- Non-prototropic tautomerism involves the relocation of a substituent other than H, e.g. the tautomerism of 1-
and 2-(N,N-disubstituted aminomethyl)benzotriazoles.
4) Ring-Chain Tautomerism
- In ring-chain tautomerism, a structural change occurs between an open-chain form and a ring form through an H-
transfer.
- This is an important process for monosaccharides such as sugars. Glucose is a well-known example, which can
exist in five different tautomeric forms in solution. Ring-chain tautomerism was first discovered by Sir Emil Fischer
in the 1890.
5) Valence Tautomerism
- Valence tautomerism involves the reorganization of bonding electrons, which results in changes in molecular
geometry.
1,3,5-cyclo-octatriene bicyclo[4.2.0]octa-2,4-diene
 Difference of Tautomerism from Resonance
1. Tautomerism involves a change in the position of atom (generally hydrogen), while Resonance involves a
change in the position of the unshared or π electron.
2. Tautomers are definite compounds and may be separated and isolated. Resonating structures are only
imaginary and can’t be isolated.
3. The two tautomeric forms have different structures (i.e. functional groups). The various resonating structures
have the same functional group.
4. Tautomers are in dynamic equilibrium with each other, resonating structures are not in dynamic equilibrium.
5. Tautomerism has no effect on bond length, while Resonance affects the bond length.
6. Tautomerism does not lower the energy of the molecule and hence does not play any role in stabilising the
molecule, while Resonance decreases the energy and hence increases the stability of the molecule.
7. Tautomerism can occur in planar as well as non-planar molecules, while Resonance occurs only in planar
molecules.
8. Tautomerism is indicated by (⇌) whereas Resonance by (⟷)
 GEOMETRIC ISOMERISM (Cis-Trans Isomerism)

- The carbon atoms of the carbon-carbon double bond are sp2 hybridized. The carbon-carbon double bonds consist
of σbond and π bond. The presence of π bond locks the molecule in one position, therefore rotation around the
C=C bond is not possible.
- This restriction of rotation obout the carbon-carbon double bond is responsible for Geometric Isomerism.
- The Cis isomers is one in which two similar groups are on the same side of the double bond.
- The Trans isomers is one in which two similar groups are on the opposite sides of the double bond.
 Overall Relative Stabilities Of Alkenes: trans isomer and cis isomer:
A. The reaction of an Alkene with hydrogen is an exothermic reaction; the enthalpy change involved is
called the heat of hydrogenation.
–1
i. Most alkenes have heat of hydrogenation near–120 kJ mol .
–1
ii. Individual alkenes have heats of hydrogenation may differ from this value by more than 8 kJ mol .
iii. The differences permit the measurement of the relative stabilities of alkene isomers when hydrogenation
converts them to the same product.
B. In each reaction:
i. The product (butane) is the same.
ii. One of the reactants (hydrogen) is the same.
iii. The different amount of heat evolved is related to different stabilities (different heat contents) of the
individual butenes.
An energy diagram for the three butenes isomers. The order of stability is trans-2-butene > cis-2-butene > 1-butene.
iv. 1-Butene evolves the greatest amount of heat when hydrogenated, and trans-2-butene evolves the least.
v. 1-Butene must have the greatest energy (enthalpy) and be the least stable isomer.
vi. Trans-2-Butene must have the lowest energy (enthalpy) and be the most stable isomer.
C. Trend of stabilities: trans isomer > cis isomer
D. The greater enthalpy of cis isomers can be attributed to strain caused by the crowding of two alkyl
groups on the same side of the double bond.
cis- and trans-Alkene isomers. The less stable cis isomer has greater strain.
E. The stability of the butenes isomers:
F. The geometric isomers of butenedioic acid

- Chemical properties of the cis- and trans- isomers are usually very similar, but an interesting exception to this is
seen with butenedioic acid. Here the two isomers have such different reactivities.
- The differences in the properties of the cis-and trans- isomers of butenedioic acid become very evident when
examples of their roles in biology are compared. Fumaric acid (trans-) is an intermediate in the Krebs cycle, an
essential part of the reactions of aerobic respiration for energy release in cells. By contrast, maleic acid (cis-) is an
inhibitor of reactions that interconvert amino acids, for example, in the human liver. Their different biological
activities are a consequence of their different shapes affecting their binding to enzymes, the biological catalysts
that control all these reactions.
G. The geometric isomers of 1,2-dichloroethene

- The polarity strongly influences the relative boiling point as it determines the strength of the intermolecular
forces.
- For example, cis-1,2-dichloroethene has a net dipole moment and dipole-dipole attractions between its
molecules in addition to the Van Der Waals' forces, whereas trans-1,2-dichloroethene which is non-polar has only
Van Der Waals' forces. The boiling point of the cis-isomer is therefore higher.
H. Cis and Trans for Cyclic molecules

- Cycloalkanes contain a ring of carbon atoms in which the bond angles are strained from the tetrahedral angles in
the parent alkane and the ring prevents rotation around the carbon atoms, so when there are two different
groups attached to two carbons in the ring, these molecules can exist as the cis- and trans- forms. For example:
 CHIRAL AND ACHIRAL MOLECULES
 A molecule (or an object) is said to be chiral or dissymmetric, if it is not superimposable on its mirror image and
the property of non-superimposability is called chirality.
 On the other hand, a molecule (or an object) which is superimposable on its mirror image is called achiral (non-
dissymmetric or unsymmetrical).
 Chiral carbon atom (chiral centre/stereo centre). Carbon atom bonded to four different atoms or groups is called
an asymmetric carbon atom or a chiral atom. A chiral atom is indicated by an asterisk (*).
 Note: Isotopes of a particular atom behave as different groups in stereoisomerism
 If a molecule contains only one chiral centre/atom, then the molecule has to be optically active (i.e. non
superimposable on its mirror image) as it will not contain any element of symmetry. Molecules containing two or
more chiral centers may or may not be chiral (optically active).
 It is necessary to distinguish chiral and chiral centre. The word chiral is used for molecule as a whole which is
optically active, whereas chiral centre is for an atom which is attached to form different atoms/groups.
Cholesterol has eight chiral centres
 Relationships between Chiral Centers and Chiral Molecules

- The term chiral center refers to an atom in the molecular structure. The term chiral molecule refers to the
entire molecule.
- The presence of one chiral center renders the entire molecule chiral. The presence of two or more chiral
centers may or may not result in the molecule being chiral. In the examples given below the chiral centers
are indicated with an asterisk. The vertical broken line represents a plane of symmetry.
Ibuprofen: One chiral center renders the cis-1,2 dimethylcyclohexane trans-1,2 dimethylcyclohexane
molecule chiral is an achiral molecule is a chiral molecule
 What is Chirality?
The property of nonsuperimposability of an object on its mirror image is called chirality. Such molecule has no
symmetry elements of the second kind. If the molecule is superposable on its mirror image, it is ACHIRAL.
 ELEMENTS OF SYMMETRY
 The types of elements of symmetry are as follows,
1. Plane of symmetry: A molecule is said to possess a plane of symmetry if the atoms or groups on one side of
the plane forms the mirror image of those on the other side. In other words, a plane which bisects a
molecule/object in two equal halves.
2. Centre of symmetry:
- A centre of symmetry in a molecule is said to exist if a line is drawn from any atom or group to this point and
then extended to an equal distance beyond this point meets the identical atom or group. A centre of
symmetry is usually present only in an even membered ring.
Meso-tartaric acid
(trans 2, 4 - dimethylcyclobutane trans 1, 3- carboxylic acid)
- So, for any compound to be optically active it must not possess any element of symmetry.
- Although in meso-tartaric acid there are two chiral centers, yet the molecule is optically inactive because it
contains plane of symmetry, i.e. presence or absence of symmetries in the molecule can be known by the
configuration of the molecule and not by its structure.
Molecule 1 and its mirror image are different. Molecule 2 and its mirror image are the same. Therefore,
Therefore, molecule 1 is chiral. molecule 2 is not chiral because there is a plane of
symmetry in molecule 2 that cuts thought the NH2 and OH
groups.
 Enantiomers & Diastereomers

Enantiomers Diastereomers
An enantiomer is one of two stereoisomers that are Diastereomers (or diastereoisomers) are stereoisomers
non-superimposable complete mirror images of each that are not enantiomers (non-superimposable mirror
other. images of each other).
Molecules must contain atleast one chiral centers. Molecules must contain more than one chiral center.
Enantiomers have, when present in a symmetric Diastereomers can have different physical properties and
environment, identical chemical and physical different reactivity. In another definition diastereomers are
properties except for their ability to rotate plane pairs of isomers that have opposite configurations at one
polarized light by equal amounts but in opposite or more of the chiral centers but are not mirror images of
directions. each other.
A mixture of equal parts of an optically active isomer Racemic mixture is not possible.
and its enantiomer is termed Racemic and has a net
rotation of plane polarized light of zero.
2-bromo-3-chlorobutane
 What are the differences between Enantiomers?

- Non superimposable mirror image isomers called enantiomers. For example D-(+)-glyceraldehyde and L-(-)-
glyceraldehyde
Physical and chemical property D-(+)-glyceraldehyde L-(-)-glyceraldehyde

25 0
Sign of optical rotation *α+D +8.7 *α+D25-8.70
Thin layer chromatography not separable, same Rf not separable, same Rf
1H NMR, 13C NMR No difference No difference
LCMS, HPLC, GCMS Same, no difference Same, no difference
Melting point, boiling point, solubility, refractive index Same, no difference Same, no difference
Rate of reaction in achiral medium Same rate of reaction Same rate of reaction
Rate of reaction in chiral medium Different in chiral medium Different in chiral medium
 What are Diastereomer / Diastereomers / Diastereoisomerism?

- Stereoisomerism other than enantiomerism.
- Diastereoisomers (or diastereomers) are stereoisomers not related as mirror images.
- Diastereoisomers are characterized by differences in physical properties, and by some differences in chemical
behavior towards achiral as well as chiral reagents.
- If two molecules are mirror images, then their configurations are exactly opposite and they are enantiomers. For
example D and L erythroses are mirror images, so they are enantiomers, same way D and L threoses are
enantiomers.
- If two molecules are not mirror images, but still they are stereoisomers they are diastereomers, D-erythrose and
D-threose are not mirror images so they are diastereomers, same way D-erythrose and L-threoses; L-erythrose
and D-threose; L-erythrose and L-threoses are diastereomeric pairs.
- Diastereomers are different geometrical entities. But enantiomers are identical geometrical entities.
- For the diastereomeric relationship chirality is not essentiality. For example cis- and trans-isomers are
diastereomers.
- Single asymmetric centre cannot show diastereoisomerism.

- Epimers are also diastereomers.
Physical and chemical property Diastereomeric pair

Sign of optical rotation Different
Thin layer chromatography separable, different Rf
1H NMR, 13C NMR Different δ values
LCMS, HPLC, GCMS different
Melting point, boiling point, solubility, refractive index different
Rate of reaction in achiral medium different
Rate of reaction in chiral medium different
 Meso Compound
- An optically inactive compound whose molecule is superimposable on its mirror image inspite of the presence of
chiral carbon atoms is called a meso compound.
- If a molecule has two or more chiral centers, it is usually chiral. The exceptions are meso‐molecules, which are
not chiral. These are molecules that due to symmetry have chiral centers that ‘cancel’ each other out.
- Has two or more chiral centers
- Has a plane of symmetry.
A person is meso (NOT CHIRAL) even though they have chiral

elements (hands and feet). There is a plane of symmetry down the
middle of a person, which makes a person the same as their mirror
image.
This molecule is meso (NOT CHIRAL). It has two chiral centers and a
plane of symmetry.
This molecule is not meso (CHIRAL). It has two chiral centers but no
plane of symmetry.
This molecule is not meso (NOT CHIRAL). It has a plane of symmetry

but no chiral centers. The carbons attached to the NH2 groups may
look like chiral centers but they are not.
In Tartaric acid:
The molecule contains two chiral carbons and the number of optical isomers should be
2n = 22 = 4 but number of optical isomer is reduced to 3 because one molecule has a plane of
symmetry. The stereoisomers of tartaric acid are,
I and II are enantiomers (non-superimposable); III and IV are meso form (superimposable).
 Calculation of number of optical isomers in compounds (containing ‘n’ chiral atoms)
Number of optical Number of meso Number of Total number

S. No. Compounds active forms forms Racemic mixture of optical
(a) (m) (a/2) isomers
1 The molecule has
no symmetry
2n 0 2n-1 a+m
2a The molecule has
symmetry:-
Case1:
When compound
2n−1 2n/2−1 2n−1/2 a+m
has even number of
chiral carbon atom
2b The molecule has
symmetry:-
Case1:
When compound
2n−1−2(n−1)/2 2n−1/2 a/2 2n−1
has odd number of
chiral carbon atom
Example:
1.
Number of optically active forms: a = 2n = 23 = 8

Number of Racemic mixture: (a/2) = 2n-1 = 23-1= 4
Total number of optical isomers: a+m = 8+0 = 8
2.
Number of optical isomer: a = 2n−1 = [22−1] = 2

Number of meso form: m = 2n/2−1 = [22/2−1] = [20] = 1
Total number of configuration isomer: a+m = [2+1] = 3
3.
Number of optical isomer: a = 2n−1−2(n−1)/2 = [23−1 – 2(3−1)/2] = [22 – 21+ = *4−2+ = 2

Number of meso form: 2n−1/2 = [23-1/2] = 2
Number of Racemic mixture: (a/2) = 2/2 = 1
Total no. of configurational isomers: 2n−1 = [23-1] = [22] = 4
 Optical Activity
 Sir Christiaan Huygens (1629-1695). Dutch astronomer, mathematician, and physicist. He discovers plane
polarized light.
 What is plane-polarized light?
- Ordinary light consists of electromagnetic waves that oscillate in all planes perpendicular to the direction in
which the light travels. Passing light through a polarizer allows light in only one plane to come through. This is
plane-polarized light (or simply polarized light), and it has an electric vector that oscillates in a single plane.
- A POLARIMETER is an instrument that allows plane-polarized light to travel through a sample tube containing
an organic compound. After the light exits the sample tube, an analyzer slit is rotated to determine the
direction of the plane of the polarized light exiting the sample tube. There are two possible results. With
achiral compounds, the light exits the sample tube unchanged, and the plane of the polarized light is in the
same position it was before entering the sample tube. A compound that does not change the plane of
polarized light is said to be optically inactive.
- With chiral compounds, the plane of the polarized light is rotated through an angle α. The angle α, measured
in degrees (°), is called the observed rotation. A compound that rotates the plane of polarized light is said to
be optically active.
- The rotation of polarized light can be in the clockwise or counterclockwise direction.

 If the rotation is clockwise (to the right from the noon position), the compound is called dextrorotatory.
The rotation is labeled d or (+).
 If the rotation is counterclockwise (to the left from noon), the compound is called levorotatory. The
rotation is labeled l or (–).
 SPECIFIC ROTATION
- The observed rotation depends on the number of chiral molecules that interact with polarized light. This in
turn depends on the concentration of the sample and the length of the sample tube. To standardize optical
rotation data, the quantity specific rotation (*α+) is defined using a specific sample tube length (usually 1 dm),
concentration, temperature (25 °C), and wavelength (589 nm, the D line emitted by a sodium lamp).
- Specific rotations are physical constants just like melting points or boiling points, and are reported in chemical
reference books for a wide variety of compounds.
α : observed rotation (o)
l : length of sample tube (dm)
c : concentration (g/mL)
dm : Decimeter
1 dm : 10 cm
 OPTICAL INACTIVITY DUE TO COMPENSATION

- The optical inactivity is also possible due to compensation. There are two types of compensation. They are,
(a) Internal compensation
(b) External compensation.
a) Internal compensation: If the rotation of polarized light caused by one half of the molecule is exactly cancelled
by equal and opposite rotation caused by the other half of the molecule and the molecule becomes optically
inactive, then the optical inactivity of molecule is due to internal compensation (within the molecule).
Example: Mesotartaric acid
b) External compensation: If two enantiomers are mixed together in equimolar amount, then the mixture
becomes optically inactive. The rotation caused by one enantiomer is exactly cancelled by other enantiomers
and is due to external compensation. The resulting optically inactive mixture is called racemic mixture.
Example: Equimolar amount of d (Dextrorotatory) and l (Levorotatory) form of tartaric acid.
 OPTICAL PURITY
- The "optical purity" is a comparison of the optical rotation of a pure sample of unknown stereochemistry versus
the optical rotation of a sample of pure enantiomer.
- An “optically pure” (or “enantiomerically pure”) solution of 100% (S,S) tartaric acid and 0% (R,R) tartaric acid will
have an optical rotation of (-)12°.
- An “optically pure” solution of 100% (R,R) tartaric acid and 0% (S,S) tartaric acid will have an optical rotation of
(+)12° .
100% optically pure l-tartaric acid has a specific rotation of –12°, which gradually rises to 0° as the proportion of
the d enantiomer is raised to 50%. As the molar composition of the d form increases, so does the optical rotation,
going up to +12° again for the optically pure d-enantiomer.
- The optical purity as the observed rotation of a mixture divided by the specific rotation of the pure enantiomer
(obtained under identical conditions).
 CONDITIONS FOR OPTICAL ACTIVITY
1) To exhibit optical activity molecule must possess asymmetric carbon: Asymmetric carbon compounds are
optically active. But, presence of asymmetric is not only the requirement.
2) To exhibit optical activity molecule must not have the symmetry elements, (a) plane of symmetry (b) centre of
symmetry (c) n-fold alternating access of symmetry. If these three are absent then only the compounds exhibits
optical activity.
(a) Plane of symmetry: A plane which bisects the molecules into two mirror images are called plane of symmetry.
If the plane of symmetry is present then the molecule is optically inactive, if absent then optically active.
(b) Centre of symmetry: If all the lines two identical groups pass through a single point or a central point is called
centre of symmetry.
(c) n-Fold alternating access of symmetry: If a rotation by 360º/n degrees (n = 1, 2, 3, …)followed by reflection in
plane perpendicular to the access taken results in identical molecule the compound said to be possess n-fold
alternating access of symmetry. If plane of symmetry or centre of symmetry is present then n-fold alternative
access of symmetry is present. If plane of symmetry or centres of symmetry are absent then n-fold alternating
access of symmetry will be absent. If the n-fold alternating access of symmetry present then the molecule is
optically inactive, if absent then optically active.
 STEREOISOMERISM IN ORGANIC COMPOUNDS

 The isomerism which arises due to different spatial arrangements of atoms or groups is called stereo isomerism. It
is broadly divided into:
i. Geometrical isomerism
ii. Optical isomerism
iii. Conformational isomerism
 The stereo isomers have same structural formula i.e., same connectivity order between atoms. However the atoms
or groups are arranged differently in space.
 CIS & TRANS GEOMETRICAL ISOMERISM
 The geometrical isomerism arises when atoms or groups are arranged differently in space due to restricted
rotation of a bond or bonds in a molecule.
 Example 1:
- Two different spatial arrangements of methyl groups about a double bond in 2-butene give rise to the
following geometrical isomers.
- Two forms are not inter convertible due to restricted rotation of double bond. In the cis isomer, the two
methyl groups are arranged on the same side of a double bond. Whereas in the Trans isomer, they are
on the opposite side.
 Example 2:
- There are two geometrical isomers (cis & trans) possible in case of 1,4–dimethylcyclohexane.
- Here the methyl groups are arranged differently about the plane of the cyclohexane ring. These isomers
are not inter convertible since it is not possible to rotate the bonds in the cyclohexane ring.
 The geometrical isomers often show different physical and chemical properties.
 The difference in their physical properties is more significant when there is more difference in their polarity.
 Usually the dipole moment of cis isomers is greater than that of trans isomers. Hence the cis isomers usually
have more solubility in polar solvents.
 In general, the Trans isomers are more stable than cis isomers.
 Geometrical isomerism in nitrogen compounds. Geometrical isomerism due to restricted rotation around > C =
N bond. The important class of compounds exhibiting geometrical isomerism due to >C=N bond are (i) oximes (ii)
hydrazones and (iii) semi carbazones.
- In aldoxime, when hydrogen and hydroxyl group are on the same side, the isomer is known as syn (analogous
to cis) and when these groups are on the opposite sides, the isomer is known as anti ( analogous to trans).
Syn-Benzaldoxime anti – Benzaldoxime

- Similarly, azo compounds show geometrical isomerism.
anti-azobenzene syn-azobenzene
 Distinction between cis and trans isomers. Distinction between cis and trans isomers of a compound can be
made on the basis of their physical properties such as melting point, boiling point, solubility, dipole moment
etc.
i. Melting point:
- In general, the melting point of a trans isomer is higher than that of the corresponding cis isomer. This is due
to the reason that the molecules of a trans isomer are more symmetrical and hence fit more closely in the
crystal lattice as compared to the molecules of a cis isomer.
- In order for the intermolecular forces to work well, the molecules must be able to pack together efficiently in
the solid. Trans isomers pack better than cis isomers. The "U" shape of the cis isomer doesn't pack as well as
the straighter shape of the trans isomer. The poorer packing in the cis isomers means that the intermolecular
forces aren't as effective as they should be and so less energy is needed to melt the molecule a lower melting
point.
ii. Solubility: In general, solubility of a cis isomer is higher than that of the corresponding trans isomer. This is
due to the reason that the molecules of a cis isomer are less tightly held in the crystal lattice.
iii. Dipole moment: The cis isomer has higher dipole moment than the corresponding trans isomer.
iv. Stability: The trans isomer is more stable than cis isomer due to steric hindrance. Intermolecular reactions
occur easily when reacting groups are close together. Hence, the cis isomer will form cyclic derivatives more
readily as against trans derivatives. But this reaction will take place in only those cis isomers in which the
substituent’s on two double bonded carbons are capable of intramolecular reaction with each other.
Note By: Fumaric acid forms anhydride via the formation of maleic acid because at high temperature fumaric acid
converts into maleic acid
v. Action of heat: On strong heating cis and trans isomers are interconvertible. This interconversion takes place as
follows:
 NUMBER OF GEOMETRICAL ISOMER IN POLYENES

a) When compound has ‘n’ double bonds and ending groups of a polyene are different, the number of
n
geometrical isomers = 2 .
Example 1: C6H5 – CH = CH – CH = CH – CH = CH – CH = CH – Cl
Since, the number of double bonds is four and two ends are different, one is C6H5 and other is Cl. Therefore,
n
Number of geometrical isomers = 2 =24 = 16
b) When the ending groups of polyene are same
n−1
Case – I: When number of double bonds is even then the number of geometrical isomers = 2 + 2n/2−1
Example 2: Cl – CH = CH – CH = CH – CH = CH – CH = CH – Cl
n = 4 (even)
n−1
Number of geometrical isomers = 2 + 2n/2−1 = 23 + 21 = 10
n−1
Case – II: When number of double bond is odd then no. of geometrical isomer = 2 + 2(n+1)/2–1
Example 3: C6H5 – CH = CH – CH = CH – CH = CH – C6H5
n = 4 (odd)
2
Number of geometrical isomers = 2 + 22−1 = 6
 E & Z NOTATION FOR GEOMETRIC ISOMERISM

 The simple convention of denoting the geometrical isomers by cis/trans descriptors is not sufficient when there
are more than two different substituents on a double bond. To differentiate the stereochemistry in them, a new
system of nomenclature known as the E & Z notation method is to be adopted.
 According to this method, if the groups with higher priorities are present on the opposite sides of the double
bond, that isomer is denoted by E. Where E = Entgegen ( the German word for 'opposite' ) or E = Enemy
 However, if the groups with higher priorities are on the same side of the double bond, that isomer is denoted by
Z. Where Z = Zusammen (the German word for 'together')
 The letters E and Z are represented within parentheses and are separated from the rest of the name with a
hyphen.
 Step by step procedure to determine the E and Z configuration: The following procedure is to be adopted to
denote the geometrical isomers by E & Z descriptors.
 First determine the higher priority group on each end of the double bond.
 If the higher priority groups are on the opposite sides of double bond, the isomer is denoted by the
descriptor, E.
 Otherwise if they are on the same side of double bond, the Z descriptor must be used.
 The priorities are assigned by following Cahn-Ingold-Prelog sequence rules:
- Rule 1: Rank the atoms directly attached to the olefinic carbon according to their atomic number. High
priority is given to the atom with higher atomic number.
Z-bromochloroiodoethene E-bromochloroiodoethene
- Rule 2: If isotopes of same element are present, the higher priority is given to the isotope with higher atomic
mass. E.g. the Deuterium isotope (H2 or D) has more priority than protium (H1 or H). The C13 isotope has
more priority than C12.
- Rule 3: If the relative priority of two groups cannot be decided by Rule 1, it shall be determined by applying
to the next atom or sequence of atoms in the group 'X'.
e.g. for typing groupings in organic molecules where X is more than one atom ....
X = -CH2CH2CH3 > -CH2CH3 > -CH3 > -H i.e. the longer the hydrocarbon carbon chain the higher its priority,
- Rule 4: Treat double and triple bond as if each were a bond to a separate atom. For this methods, imagine
that pi (π) bond is broken and the atoms at both ends duplicate. (or) Atoms participating in double/triple
bonds are considered to be bonded to an equivalent number of similar “phantom” atoms by single bonds.
Note: “phantom” atoms are bonded to no other atoms.
 D & L-System
- The D & L convention, not to be confused with the d (dextro) and l (levo) descriptors used to designate the
direction of specific rotation of chiral compounds, is a convention used to distinguish between enantiomers of
chiral monosaccharides and chiral alpha-amino acids, based on the molecule drawn as a Fischer projection in a
specific orientation.
- The L and D forms of the sugar depends on the orientation of the -H and -OH groups around the carbon atom
adjacent to the terminal primary alcohol carbon (carbon 5 in glucose) determines whether the sugar belongs to
the D or L series.
- The D- and L- notation is based on glyceraldehyde.
- When the -OH group on this carbon is on the right, then sugar is the D-isomer; when it is on the left, then it is the
L-isomer.
- Most of the monosaccharide occurring in mammals is D sugars, and the enzymes responsible for their
metabolism are specific for this configuration. In solution, glucose is dextrorotatory-hence the alternative name
dextrose.
- The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-
polarized light is passed through a solution of an optical isomer, it will be rotated either to the right,
dextrorotatory (+); or to the left, levorotatory (-). The direction of rotation is independent of the stereochemistry
of the sugar, so it may be designated D (-), D (+), L (-), or L (+). For example, the naturally occurring formof
fructose is the D (-) isomer.
D-Tagatose is an epimer of D-fructose inverted at C-4
 Application of D,L convention to monosaccharides:

- One enantiomer of a chiral monosaccharide is labeled D and the other L. To determine whether a given
enantiomer of a chiral monosaccharide is D or L, use the following procedure.
 Step 1: Make sure the acyclic form of the molecule is drawn as a Fischer projection. If the monosaccharide
is an aldose, the aldehyde group must be on top; if it is a ketose, the carbonyl carbon must be the second
carbon from the top.
Aldose Sugar (Glucose) Ketose Sugar (Fructose)
 Step 2: Number the carbon atoms starting at the top.
Aldose Sugar (Glucose) Ketose Sugar (Fructose)
 Step 3: Locate the carbon atom that bears the second highest number, which is known as the penultimate
carbon. If the hydroxy group on the penultimate carbon is on the right of the carbon chain, assign the label
D to the compound; if it is on the left of the carbon chain, assign the label L.
D-Glucose L-Fructose
 The enantiomer of a given chiral monosaccharide, simply draw its mirror image.
- Application of D,L convention to alpha-amino acids:

- One enantiomer of a chiral alpha-amino acid is labeled D and the other L. To determine whether a given
enantiomer of a chiral alpha-amino acid is D or L, use the following procedure.
 Step 1: Make sure that the molecule is drawn as the Fischer projection in which the carboxylic acid group is
on top and the side chain on bottom.
 Step 2: If the amine group is on the right of the carbon chain, assign the label D to the compound; if it is on
the left of the carbon chain, assign the label L.
 To draw the enantiomer of a given chiral alpha-amino acid, simply draw its mirror image.
- Note By: What is the PENULTIMATE CARBON?

- Penultimate means next to last.
- The penultimate (second to last carbon) carbon is the last chiral carbon of the chain.
 Alpha () and Beta () Anomers

- An anomer is a type of geometric variation found at certain atoms in carbohydrate molecules.
- An anomer is an epimer at the hemiacetal/acetal carbon in a cyclic saccharide, an atom called the anomeric
carbon.
- Anomerization is the process of conversion of one anomer to the other.
 Cyclic Structures and Anomeric Forms
- Alcohols react readily with aldehydes to form hemiacetals:
 This reaction is promoted in the presence of either acid or base
 One of the subtleties of this reaction involves the stereochemistry of the aldehyde and keto carbon it goes
from being achiral to chiral.
- Similarly alcohols react with ketones to produce hemiketals:
- Since aldoses and ketoses contain alcohol groups, in addition to their aldehyde or ketone groups, they have the
potential to react to form cyclic forms.
- Cyclization creates an anomeric carbon (the former carbonyl carbon), generating the α and β configurations of
the sugar, for example, α-D-glucopyranose and β-D-glucopryanose.
- These two sugars are both glucose but are anomers of each other.
- In the α configuration, the OH on the anomeric C projects to the same side as the ring in a modified Fischer
projection formula. In a Haworth projection formula of the α configuration, this OH is trans to the CH2OH group.
- Since the α and β forms are not mirror images, they are referred to as diastereomers.
- Enzymes are able to distinguish between these two structures and use one or the other preferentially. For
example, glycogen is synthesized from α-D-glucopyranose, whereas cellulose is synthesized from β-D-
glucopyranose.
- The cyclic α and β anomers of a sugar in solution are in equilibrium with each other and can be spontaneously
interconverted which is known as mutarotation.
 ANOMERIZATION
- It is the process of conversion of one anomer to the other. For reducing sugars, anomerization is referred to as
mutarotation and occurs readily in solution and is catalyzed by acid and base.
- This reversible process typically leads to an anomeric mixture in which eventually an equilibrium is reached
between the two single anomers.
- The ratio of the two anomers is specific for the regarding sugar. For example, regardless of the configuration of
the starting D-glucose, a solution will gradually move towards being a mixture of approximately 64% β-D-
glucopyranoside and 36% of α-D-glucopyranose. As the ratio changes, the optical rotation of the mixture
changes; this phenomenon is called Mutarotation.
 MUTAROTATION
- Mutarotation is the change in the optical rotation because of the change in the equilibrium between two
anomers, when the corresponding stereocentre interconvert.
- Cyclic sugars show Mutarotation as α and β anomeric forms interconvert.
- The optical rotation of the solution depends on the optical rotation of each anomer and their ratio in the solution.
- Example:
o In the “alpha” (α) anomer, the OH group on C-1 is on the opposite side of the ring as the chain on C-5.
o In the “beta” (β) anomer, the OH group on C-1 is on the same side of the ring as the C-5
o The alpha (α) anomer of D-glucose has a specific rotation of +1120 in water.
o The beta (β) anomer of D-glucose has a specific rotation of +190. (18.7 actually, but rounding up to 19).
o When either anomer is dissolved in water, the value of the specific rotation changes over time, eventually
reaching the same value of +52.50.
o The specific rotation of α-D-glucopyranose decreases from +1120 to +52.50.
o The specific rotation of β-D-glucopyranose increases from +190 to +52.50.
o This behaviour is called mutarotation
 Epimers
- Those stereoisomers which are differing in its configuration at only one chiral carbon atom are called as Epimers.
- Epimers are diastereomers that contain more than one chiral center but differ from each other in the absolute
configuration at only one chiral center.
- In epimers the chiral carbon atoms whose absolute configuration makes the two compounds different are called
the epimeric carbons.
Alpha and beta glucose are epimers of one another.
 EPIMERISATION
- The chemical conversion of one epimer to another is called epimerization.
- If this interconversion is catalyzed by an enzyme, the enzyme is an epimerase.
a) Enolate Mechanism
b) Enediol Mechanism
 ISOMERIZATION
- Isomerization (also isomerisation) is the process by which one molecule is transformed into another molecule
which has exactly the same atoms, but the atoms have a different arrangement e.g. A-B-C → B-A-C (these related
molecules are known as isomers).
- Enediol Rearrangement: The position of carbonyl group may shift via enediol intermediate under basic
condition. For example, rearrangement of D-glucose gives D-fructose.
Conversion of glucose to mannose is epimerization (Base-Catalyzed Epimerization of Glucose)
 Racemic Mixture & Racemization

 RACEMIC MIXTURE
- A racemic mixture is a 1:1 mix of two enantiomers (Each of a pair of molecules that are mirror images of each
other).
- No matter how many molecules are in a mixture, it is racemic if there are equal numbers of the two enantiomers.
- The racemic mixture produces a net optical rotation - of plane polarized light - of zero degrees. This is because
the mixture contains equal amounts - equimolar mixture - of both enantiomers that have opposite rotations.
- A racemic mixture is a solution containing equal amounts of a pair of enantiomers.
- Note By:
o A solution containing equal amounts of (R)-2-butanol and (S)-2-butanol is a racemic mixture.

o A solution containing an excess of either the (R)-enantiomer or the (S)-enantiomer would be
ENANTIOENRICHED.
o A solution containing only the (R)-enantiomer or the (S)-enantiomer will be ENANTIOMERICALLY PURE.
 RESOLUTION OF RACEMIC MIXTURES

- The separation of a racemic mixture into the individual enantiomerically pure enantiomers is called resolution.
- Since enantiomers have identical physical properties, such as solubility, boiling point and melting point, they
cannot be resolved by common physical techniques such as direct crystallization, distillation or basic
chromatography.
- The main difficulty in a process of resolution is that d or (+) and l or (–) forms have identical physical and chemical
properties, so they cannot be separated by ordinary methods. However, the following methods can be used for
this purpose.
(i) Mechanical separation:
 If the d or (+) and l or (–) forms of a substance exits in well-defined crystalline forms, the separation can be
done by hand picking with the help of magnifying lens and a pair of tweezers.
 For example, the d and l forms of sodium ammonium tartarate can be separated by this method.
 The method has very limited application and applies to only few crystalline constituents having different
shape.
(ii) Biochemical separation:
 In this method, the resolution is done by the use of microorganisms.
 When certain bacteria or moulds are added to a solution of a racemic mixture, they decompose one of the
optically active forms more rapidly than the other.
 For example, when the mould, racemic ammonium tartarate, the mould completely decomposes the d form
white l form is left practically unaffected. The main drawback of the method is that half of the material is
destroyed during resolution. The process is very slow and only small amounts of the materials can be
separated.
(iii) Chemical separation:
 This is probably the best method of resolution. The racemic mixture is made to combine with another
optically active compound and the resulting solubility in various solvents.
 By fractional crystallization from a suitable solvent, they can be separated.
 For example, the racemic mixture of lactic acid is allowed to combine with the optically active base (-)
strachnine or (+) brucine.
- Example of Resolution of Racemic Mixtures
(i) (S)-1-Phenylethylamine combines with a racemic mixture of lactic acid to form diastereomeric salts. The
diastereomers are separated by fractional crystallization.
o After the separation process, each of the diastereomers is subsequently treated with a strong acid such as
hydrochloric acid to regenerate the corresponding enantiomer of lactic acid
o Note that the lactic acid would be soluble in the organic layer, while the ammonium salt would be in the
water layer.
o Since enantiomerically pure compounds are very expensive, it is usually necessary to recover and reuse the
chiral amine. This is achieved by treating the (S)-1-phenylethyl ammonium chloride salt with a base such as
sodium hydroxide to regenerate and recover the chiral amine.
 RACEMIZATION
- Racemization is the conversion of an enantiomerically pure mixture (one where only one enantiomer is present)
into a mixture where more than one of the enantiomers are present. (Or) Conversion of an optically active
substance to a raceme.
- Optically active carbonyl compounds of the type −CHC=O , in which the alpha carbon is asymmetric, are
racemized by both acids and bases
- The racemization of an optically active secondary halide with the chiral carbon carrying the halogen (e.g., 2-
chlorobutane) may occur in the solution and, usually, the more polar and better ionizing the solvent is, the more
readily the substance is racemized. Ionization of the halide by an SN1 process probably is responsible, and this
certainly would be promoted by polar solvents. All indications are that an alkyl carbocation once dissociated from
its accompanying anion is planar; and, when such an ion recombines with the anion, it has equal probability of
forming the D and L enantiomers:
 Atropisomerism
- Biphenyls are compounds whereby a phenyl ring is connected to another through a central σ bond.
- In unsubstituted biphenyl, there is sufficient amount of freedom of rotation around the central single bond to
allow for free interconversion between the various conformers or rotamers so that the various rotamers cannot
exist independently.
- However, biphenyls with large substituents at the ortho positions on either side of the central σ bond experience
restricted rotation along this bond due to steric hindrance. If the substituents are different, a chiral molecule
existing as a pair of enantiomers called atropisomers is obtained.
- Polynuclear aromatic systems such as binol also exist as enantiomers.
- Atropisomerism are stereoisomers as a result of restricted rotation about a single bond.

- Atropisomers are stereoisomers resulting from hindered rotation about single bonds where the steric strain
barrier to rotation is high enough to allow for the isolation of the conformers (from Greek, a = not and tropos =
turn).
- If bulky group on ortho position of bi-phenyl or strained ring structural features. Bulky substituents or strained
rings may enhance the barrier to rotation between two distinct conformations to such an extent as to allow
observation of atropisomers.
- Atropisomerism is also called axial chirality and the chirality is not simply a centre or a plane but an axis.
- Biphenyl substituted on ortho position, which contains a chiral axis along the biphenyl linkage. The biphenyl rings
are perpendicular to each other in order to minimize steric clashes between the four ortho substituents meaning
that rotation about the biphenyl bond through pivotal bond is restricted.
- Conditions of Atropisomerism:
1. A rotationally stable axis
2. Presence of different substituents on both sides of the axis
3. The configurational stability of axially chiral biaryl compounds is mainly determined by three following
factors:
i. The combined steric demand of the substituent in the combined steric demand of the substituents in
the proximity of the axis.
ii. The existence, length and rigidity of bridges.
iii. Atropisomerisation mechanism different from a merely physical rotation about the axis, e.g. photo
chemically or chemically induced processes.
- Stereochemical assignment
o Determining the axial stereochemistry of biaryl atropisomers can be accomplished through the use of a
Newman projection along the axis of hindered rotation.
o The ortho, and in some cases meta substituents are first assigned priority based on Cahn–Ingold–Prelog
priority rules.
o Starting with the substituent of highest priority in the closest ring and moving along the shortest path to the
substituent of highest priority in the other ring, the absolute configuration is assigned P or Δ for clockwise
and M or Λ for counterclockwise.
 Fischer Projection
- Fischer Projections are abbreviated structural forms that allow one to convey valuable stereochemical
information.
- The definition is that every carbon is specified completely by a cross designating the carbon (at the center) and
the four bonds to that carbon. The stereochemistry of the bonds is defined (now) as the horizontal bonds are in
front of the plane (coming toward you, the viewer); the vertical bonds are behind the plane (going away from
you).
- When relating one Fischer projection to another, it's important to realised that it may only be manipulated within
the 2D plane
- Why we can't rotate 900? A 900 rotation is equivalent to breaking bonds and exchanging two groups, which
would result in the formation of the other enantiomer.
- Fischer projections a can also be used to represent molecules with more than one chirality center.
- A Fischer projection or Fischer projection formula is a convention used to depict a stereo-formula in two
dimensions without destroying the Stereochemical information, i.e., absolute configuration, at chiral centers.
o To convert this stereoformula into a Fischer projection use the following procedure
[Fischer Projection of (R)-Lactic acid]
Step 1: Hold the molecule so that

(i) The chiral center is on the plane of the paper,
(ii) Two bonds are coming out of the plane of the paper and are on a horizontal plane,
(iii) The two remaining bonds are going into the plane of the paper and are on a vertical plane.
Step 2: Push the two bonds coming out of the plane of the paper onto the plane of the paper.
Step 3: Pull the two bonds going into the plane of the paper onto the plane of the paper.
Step 4: Omit the chiral atom symbol for convenience.
 Absolute configuration: R,S-System

- An absolute configuration refers to the spatial arrangement of the atoms of a chiral molecular entity (or group)
and its Stereochemical description e.g. R (Rectus) or S (Sinister).
- The arrangement of atoms in an optically active molecule, based on chemical interconversion from or to a known
compound, is a relative configuration. Relative, because there is no way of knowing just by looking at a
structure whether the assignment of (+) or (-) is correlated to a particular isomer, R or S.
- R and S notations are used only to describe asymmetric molecules following Cahn-Ingold-Prelog (CIP) sequence
rules.
(a) Rule I: first we assign the priority numbers to the four atoms/groups attached to chiral centre according to
CIP rules. For example in the case of CHClBrI, the four atoms attached to the chiral center are all different
and priority will be given based on atomic weight, thus the priority follows as I, Br, Cl, H.
(b) Rule 2: If two or more of the atoms that are bonded directly to the chiral center are the same, then prioritize
these groups based on the next set of atoms (i.e., atoms adjacent to the directly bonded atoms). Continue
until priorities can be assigned. Priority is assigned at the first point of difference.
 If two atoms have substituents of the same priority, higher priority is assigned to the atom with more of
these substituents.
 A larger group (i.e., more atoms) may not necessarily have a higher priority over another (smaller) group.
(c) Rule 3: Atoms participating in double/triple bonds are considered to be bonded to an equivalent number of
similar “phantom” atoms by single bonds. Note: “phantom” atoms are bonded to no other atoms.
(d) Rule 4: In Fischer projection representations orient the molecule so that the least priority group must be on
lower end of vertical line. If the lower priority group on horizontal line or upper side on vertical line, then to
bring the group on to vertical line do two mutual exchanges of groups so that the least priority group come
to lower end of vertical line.
(e) Rule 5: After giving priority order for the groups at asymmetric centre, if priority direction is clockwise the
configuration is specified ‘R’ (Latin: rectus, right); if anticlockwise the configuration is specified ‘S’ (Latin:
sinister, left).
(f) Rule 6: Orient the molecule in space so that the lowest priority group (#4) is directed away from you. The
three remaining groups then project toward you.
 Stereospecific and Stereoselective Reactions

 STEREOSPECIFIC REACTIONS
- A stereospecific reaction is one which, when carried out with stereoisomeric starting materials, gives a product
from one reactant that is a stereoisomer of the product from the other.
- 'Stereospecific' relates to the mechanism of a reaction, the best-known example being the SN2 reaction, which
always proceeds with inversion of stereochemistry at the reacting centre.
- Stereospecificity in substitution reactions :
SN1 mechanism non-stereospecific
SN2 mechanism stereospecific
 STEREOSELECTIVE REACTIONS
- A stereoselective process is one in which one stereoisomer predominates over another when two or more may
be formed.
- If more than one reaction could occur between a set of reactants under the same conditions giving products that
are stereoisomers and if one product forms in greater amounts than the others, the overall reaction is said to be
stereoselective.
- A stereoselective reaction in which the possible products are enantiomers is said to be Enantioselective.
- A stereoselective reaction in which the possible products are diastereomers is said to be Diastereoselective.
- Regioselective: If more than one reaction could occur between a set of reactants under the same conditions
giving products that are constitutional isomers and if one product forms in greater amounts than the others, the
overall reaction is said to be regioselective.
- Chemoselective: If an organic compound contains more than one different functional groups or more than one
like functional groups that are not equivalent (see equivalent ligands), and, if a reagent reacts exclusively or
predominately with one of them, the reaction is said to be Chemoselective.
 Difference Between Stereospecific and Stereoselective Reactions

Stereospecific Reactions Stereoselective Reactions
A stereospecific reaction is a reaction in
A stereoselective reaction is a reaction in which
which the stereochemistry of the there is a choice of pathway, but the product
Definition reactant completely determines the stereoisomer is formed due to its reaction
stereochemistry of the product without pathway being more favorable than the others
any other option. available.
A stereospecific reaction gives a specific
A stereoselective reaction can result in multiple
Number of Products
product from a certain reactant. products.
The selectivity of the reaction pathway depends
The final product of a stereospecific
on differences in steric effects (presence of bulky
Effects reaction depends on the stereochemistry
groups cause steric hindrance) and electronic
of the reactant.
effects.
 What is C. I. P. system or CIP priority and what are their rules?

- It is a short form for Cahn-Ingold-Prelog (CIP) priority rules system. CIP system or CIP conventions are a set of
rules used to name the stereoisomers of a molecule. A molecule may contain any number of stereocentre and
any number of double bonds and each gives rise to two possible configurations.
- The purpose of the CIP system is to assign ‘R’ (Rectus means clock wise) and ‘S’ (Sinister means anti-clock wise)
descriptor to each sterocenter and an ‘E’ or ‘Z’ descriptor to each double bond so that the configuration of the
entire molecule can be specified uniquely by including the descriptors in its systematic name.
- The CIP sequence rules are:
1) Rule 1: Give priority (numbering) to the groups at the asymmetric centre based on atomic weight of an atom
which is directly attached to asymmetric centre, i.e. more atomic weight atom given first priority.
2) Rule 2: If atomic weights of directly attached atoms are same, then chose other atoms in the group in
sequence, e.g. CH2CH3 is more priority then CH3
3) Rule 3: If multiple bonded groups attached to asymmetric centre do the duplication and triplication of the
group.
4) Rule 4: If asymmetric centre attached ‘R’ and ‘S’ configuration groups, then the carbon having ‘R’
configuration should be given priority over ‘S’.
5) Rule 5: if there is a ‘E’ and ‘Z’ configuration groups at asymmetric centre then the carbon with ‘Z’ should be
given more priority over ‘E’.
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UNIT –I & II Stereochemistry Isomerism & Geometrical Isomerism BP401T

Presentation · December 2018

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- There are two isomeric compounds with molecular formula C2H6O:

Simple flowchart for classifying various kinds of isomers

 STRUCTURAL ISOMERISM or CONSTITUTIONAL ISOMERS

 Number of possible chain-isomers for Alkane

 Physical Constants of the Hexane Isomers

Physical Constants of the Index of

C6H14 –153.7 60.3 1.3714

C6H14 –118 63.3 1.3765

C6H14 –128.8 58 1.3750

C6H14 –98 49.7 1.3688

1H and 2H tautomers of imidazole

 Difference of Tautomerism from Resonance

 GEOMETRIC ISOMERISM (Cis-Trans Isomerism)

 Overall Relative Stabilities Of Alkenes: trans isomer and cis isomer:

C. Trend of stabilities: trans isomer > cis isomer

E. The stability of the butenes isomers:

F. The geometric isomers of butenedioic acid

G. The geometric isomers of 1,2-dichloroethene

H. Cis and Trans for Cyclic molecules

Cholesterol has eight chiral centres

 Relationships between Chiral Centers and Chiral Molecules

 Enantiomers & Diastereomers

 What are the differences between Enantiomers?

Physical and chemical property D-(+)-glyceraldehyde L-(-)-glyceraldehyde

 What are Diastereomer / Diastereomers / Diastereoisomerism?

- Single asymmetric centre cannot show diastereoisomerism.

Physical and chemical property Diastereomeric pair

A person is meso (NOT CHIRAL) even though they have chiral

This molecule is not meso (NOT CHIRAL). It has a plane of symmetry

 Calculation of number of optical isomers in compounds (containing ‘n’ chiral atoms)

Number of optical Number of meso Number of Total number

Number of optically active forms: a = 2n = 23 = 8

Number of optical isomer: a = 2n−1 = [22−1] = 2

Number of optical isomer: a = 2n−1−2(n−1)/2 = [23−1 – 2(3−1)/2] = [22 – 21+ = *4−2+ = 2

- The rotation of polarized light can be in the clockwise or counterclockwise direction.

 OPTICAL INACTIVITY DUE TO COMPENSATION

 STEREOISOMERISM IN ORGANIC COMPOUNDS

Syn-Benzaldoxime anti – Benzaldoxime

- Similarly, azo compounds show geometrical isomerism.

 NUMBER OF GEOMETRICAL ISOMER IN POLYENES

 E & Z NOTATION FOR GEOMETRIC ISOMERISM

D-Tagatose is an epimer of D-fructose inverted at C-4

 Application of D,L convention to monosaccharides:

Aldose Sugar (Glucose) Ketose Sugar (Fructose)

 Step 2: Number the carbon atoms starting at the top.

Aldose Sugar (Glucose) Ketose Sugar (Fructose)

- Application of D,L convention to alpha-amino acids:

- Note By: What is the PENULTIMATE CARBON?

 Alpha () and Beta () Anomers

- Similarly alcohols react with ketones to produce hemiketals:

Alpha and beta glucose are epimers of one another.

Conversion of glucose to mannose is epimerization (Base-Catalyzed Epimerization of Glucose)

 Racemic Mixture & Racemization

o A solution containing equal amounts of (R)-2-butanol and (S)-2-butanol is a racemic mixture.

 RESOLUTION OF RACEMIC MIXTURES

- Atropisomerism are stereoisomers as a result of restricted rotation about a single bond.

Step 1: Hold the molecule so that

Step 4: Omit the chiral atom symbol for convenience.