Introducing VarSeq Dx as a Medical Device in the European Union
Stereochemistry & Asymmetric Synthesis.pptx
1. STEREOCHEMISTRY & ASYMMETRIC
SYNTHESIS
SUBMITTED TO :- DR VIRENDRA KAUR
SUBMITTED BY :- SHWETA PANDEY
CLASS :- M. PHARMA 2ST SEM.
BRANCH :- PHARMACEUTICAL CHEMISTRY
SUBJECT :-ADVANCED ORGANIC CHEMISTRY - II
SUBJECT CODE :- MPC 202 T
2. Content Of Presentation
Basic concepts in stereochemistry –
1. Optical Activity,
2. Specific Rotation,
3. The Cahn Ingold Prelog (CIP) Sequence
Rule,
4. Meso Compounds,
5. Pseudo Asymmetric Centres ,
6. Axes Of Symmetry,
7. Fischers D And L Notation,
8. Cis -trans Isomerism,
9. E And Z Notation.
3. Content Of Presentation
Methods of asymmetric synthesis using chiral pool,
chiral auxiliaries and
catalytic asymmetric synthesis,
enantiopure separation and
Stereo selective synthesis with examples.
5. Introduction
Stereochemistry is the study of the three-
dimensional structure of molecules. It also define
as the branch of chemistry that concerned with the
three-dimensional arrangement of atoms and
molecules and the effect of this on chemical
reactions.
6.
7.
8. Introduction
Starch and cellulose are two polymers that belong
to the family of biomolecules called carbohydrates.
Cellulose and starch are both composed of the
same repeating unit .
Starch and cellulose are isomers because they are
different compounds with the same molecular
formula(C6H10O5)n
They are stereoisomers because only the three-
dimensional arrangement of atoms is different.
9. In cellulose, the O atom joins
two rings using two
equatorial bonds
. In starch, the O atom
joins two rings using
one equatorial and
one axial bond.
11. History Of Stereochemistry
Historical perspective
Christiaan Huygens(1629-
1695). Dutch astronomer,
mathematician, and physicist.
He discovered plane polarized
light
15. Historical Perspective
Jean Baptiste Biot (1774-
1862)In 1815, he noted that
certain natural organic
compounds (liquids or
solutions) rotate plane
polarized light (Optical
Activity).
16. Tartaric Acid (Racemic Acid) Obtained From
Grape Juice Fermentation)
Louis Pasteur (1822-1895)In 1847, he
repeated earlier work on Racemic Acid.
Crystallization of sodium ammonium salt
gives mirror image crystals that he
separated by hand. Equimolar solutions
of separated crystals have equal but
opposite optical activity:
17.
18. CONT….
In 1874, they proposed Carbon with 4
attachments is Tetrahedral. A molecule
having a tetrahedral carbon with 4 different
attachments may exist as a pair of isomers.
19.
20.
21. The Two Major Classes Of Isomers
Constitutional Isomers
Differ in the way the atoms are connected to each
other
Have different IUPAC names
Have same or different functional groups
Have different physical properties, so they are
separable by physical techniques such as
distillation
Have different chemical properties.
23. The Two Major Classes Of Isomers
Stereoisomers
Differ only in the way atoms are oriented in space
Stereoisomers have identical IUPAC names
(except for a prefix like cis or trans), same physical
properties .
Because they differ only in the 3D arrangement of
atoms, stereoisomers always have the same
functional group(s).
25. Configuration And Conformation
Structures that can be interconverted simply by
rotation about single bonds are conformations of
the same molecule ,
Structures that can be interconverted only by
breaking one or more bonds have different
configurations, and are stereoisomers
28. Geometrical Isomerism – GI
These isomers result from restricted rotation.
Restricted rotation can be caused by either a
cyclic structure or a double bond.
29. Geometrical Isomerism – GI
Conditions of geometrical isomerism
(1) Geometrical isomerism arises due to the
presence of a double bond or a ring structure
C=N
Nitren
e
1 methyl cyclobutane
30. Geometrical Isomerism – GI
(2) Different groups should be attached at
each doubly bonded atom.
36. Cis -Trans Isomerism
Cis /trans isomerism (also known as geometric
isomerism, configuration isomerism) is a form of
stereoisomerism describing the orientation of
functional groups within a molecule.
In general, such isomers contain double bonds,
which cannot rotate, but they can also arise from
ring structures, wherein the rotation of bonds is
greatly restricted.
37. Cis And Trans Isomers
Cis and trans isomers can be separated from each
other because they are different compounds with
different physical properties for example, they have
different boiling points and different dipole
moments
38. Requirements For Cis-trans Isomerism
1. There should be a double bond in the
molecule
.2. The two atoms or groups attached to each
doubly bonded carbon atom should be
different.
39. Cis And Trans Isomers
If the two similar groups are on same side of
restricted bond the configuration is cis otherwise
trans
Which isomer is cis and which is trans?
40. The Cahn Ingold Prelog (CIP) Sequence Rule
Absolute configuration refers to the spatial
arrangement of atoms within a chiral molecular
entity (or group) and its resultant stereochemical
description.
it was the method given by the Cohn – Ingold-
Prelog hence it is known as CIP nomenclature
The purpose of the CIP system is to assign
an R or S descriptor
41. (CIP) Sequence Rule
If the path traced from 1-2-3
clockwise = "R" enantiomer
counter clockwise = "S" enantiomer
42. (CIP) Sequence Rule
Rule I The group with the first atom having higher atomic
number is senior.
According to this rule the seniority of atoms is:
I > Br > Cl > S > F > 0 > N > C > H
Rule II The higher mass isotope is senior.
(a) T>-D>-H (b) -C14H3 > - C13H3
Rule III If the first atom of group is identical then second atom
is observed for seniority.
CH₃Cl > CH₃OH > CH3NH2
43.
44. (CIP) Sequence Rule
Rule IV To assign a priority to an atom that is part of
a multiple bond, treat a multiply bonded atom as an
equivalent number of singly bonded atoms.
45. CONT….
When the #4 priority is on a wedge you can just
reverse the rules. So now we have two sets of
rules :
If the #4 priority is on a dash :
Clockwise = R
Counterclockwise = S
If the #4 priority is on a wedge, reverse the
typical rules :
Clockwise = S
Counterclockwise = R
46. E Z-naming In G.I.
If the two senior groups are on same side of
restricted bond the configuration is Z (Z =
zusammen = together) otherwise E (E= entgegen
opposite).
•The E isomer has the two higher priority groups on the opposite sides.
• The Z isomer has the two higher priority groups on the same side.
50. Optical Isomers
Ordinary light is an electromagnetic wave,
which has oscillation in all the directions
perpendicular to the path of propagation.
When ordinary light is passed through Nicol
prism it has all its oscillations in the same
plane and is called plane- polarised light
53. Optical compounds
Certain compounds rotate the plane of
polarised light in a characteristic way when it
is passed through their solutions. These
compounds are referred to as optically active
compounds .
54. Rotation
Dextrorotatory
compounds
If the substance rotates
plane- polarised
towards the right i.e.
in clockwise direction
it is called
dextrorotatory &
indicated by 'd' or (+).
Laevorotatory
compounds
If light is rotated
towards left i.e. in
anticlockwise direction
the substance is said to
be laevorotatory and
indicated by 'l‘ or (-).
55. Specific Rotation
Specific rotation is the number of degrees of
rotation observed if a 1-dm (10-cm) tube is used
and the compound has concentration 1 gm/ml
[α ] = Specific rotation
θ =observed rotation (degree)
l = Pathlength (dm)
C=concentration (gm/ml)
λ=wavelength (nm)
t=temperature (25°C)
or
56. EX
The observed rotation of 10.0g of (R)-2-methyl-1-
butnaol in 50mL of solution in a 20-cm polarimeter
tube is +2.3° at 20 °C, what is the specific rotation of
the compound?
Answer
l= 20-cm (1-dm (10-cm) = 2
‘α’= +2.3°
C= m/V, m is the mass of the solute dissolved,
V is the total volume of the solution.
C=10/50=0.2
57. Cause Of Optical Activity
Asymmetry of the molecule is responsible for
optical activity in organic compounds
For any active molecule should not be
symmetry
58.
59. AXES OF SYMMETRY
Plane of Symmetry: (Mirror Plan)
Centre of symmetry: (Inversion Centre)
Alternating Axis of Symmetry (Improper
rotation axis)
60. Plane Of Symmetry: (Mirror Plan)
A plane of symmetry is a imaginary plane that
passes through a molecule such that atoms or
groups of atoms on one side of plane form a mirror
image of those on the other side.
It is particularly useful if
the molecule contains
two or more chiral centres .
61.
62.
63.
64.
65. Centre Of Symmetry: (Inversion Centre)
A centre of symmetry is defined as a point in a
molecule from which lines when drawn on opposite
sides at equal distance, meet exactly similar points
(groups or atoms) in the molecule.
66.
67.
68. Alternating Axis Of Symmetry (Improper
Rotation Axis)
A molecule is said to possess an n-fold alternating
axis of symmetry if, on rotating through an angle of
360° about this axis and followed by a reflection of
the resulting molecule in a plane perpendicular to
the axis, then the mirror image is exactly identical
to the original molecule.
69.
70. Asymmetric And Dissymmetric Compounds
A molecule which does not possess any element of
symmetry (there are all 23 elements of symmetry)
is called asymmetric.
A molecule which does not possess plane of
symmetry and centre of symmetry is called
dissymmetric.
71. Chirality & Enantiomers
A chiral object is one that can't be superimposed on
its mirror image
An achiral object is one that is superimposable on
its mirror image
72. Chirality & Enantiomers
Nonsuperimposable mirror-image molecules
are called enantiomers .
A chiral compound always has an
enantiomer (a non-superimposable mirror
image).
Enantiomers always exist in pairs and are
optically active .
One will be dextrorotatory (+) & other
laevorotatory (-) .
73. Meso Compounds,
Meso Compounds having atleast two chiral
carbons and have plane of symmetry or
center of symmetry or both is called meso
compounds.
Rotation of first half is cancelled by rotation
due to second half within the molecule, so it
is optically inactive due to internal
compensation
75. Criteria For Meso Compund
They are achiral (optical rotation = 0)
They have [a] = 0 due to internal
compensation of optical rotation
Presence of more than one asymmetric 'C'
atoms, no chiral center no meso .
They are non resolvable (optically inactive
compounds are non- resolvable).
76. Internal Compensation
In meso tartaric acid the inactivity is due to effects
within the molecule and not external .
The amount of rotation due to first half of the
molecule is cancelled by the opposite and equal
The optical inactivity so produced is said to be due
to internal compensation
77. Pseudo Chiral Carbon/Pseudo Asymmetric
Centre
The carbon atom which is chiral just because of
difference in configuration between two identical
groups attached to carbon is called PSEUDO
CHIRAL CARBON.
A pseudo-asymmetric centre is found in a meso
molecule where a plane of symmetry runs through
a stereogenic centre
Pseudo assymetric center is the carbon that show
chirality and achirality simultaneously. The r/s (not
R/S) nomenclature
81. D & L Nomenclature
Used for Carbohydrates & amino acids.
Glyceraldehyde is taken as reference unit.
If OH is on right hand side D
If OH is on Left hand side L
82. D & L Nomenclature
Used for Carbohydrates & amino acids.
Serine is taken as reference unit.
If NH2 is on right hand side D
If NH2 is on Left hand side L
