Pharmaceutical organic chemistry 3 B.Pharm IV SEM

1. UNIT 1

2. ISOMERISM
❖ Organic compounds which have identical molecular
formula but different in molecular structures, physical
and chemical properties or different in spatial
arrangement are called isomers and this phenomenon is
known as Isomerism.

3. Isomerism
Structural/
constitutional
isomerism
Stereoisomerism
Positional
Chain
Functional
Meta isomerism
Tautomerism
Conformational Configurational

4. ❖ It has same molecular formula but different molecular structure.
❖ Further classified as chain, positional, functional, metamerism, tautomerism and
ring chain isomerism.
1.Chain isomerism:
❑ Identical molecular formula but different arrangement of a molecular carbon
skeleton.
❑ eg. Butane M.F: C4 H10
n-butane and isobutane

5. 2.Positional isomerism:
❑ Identical carbon skeleton and identical functional groups but position of functional groups
are different in the carbon chain.
❑ eg. Butanol M.F: C4 H11 O
Butan-1-ol and Butan-2-ol
3.Funcional isomerism:
❑ Identical molecular formula but different functional groups.
❑ eg. Alcohol and ether M.F: C2 H6 O
Ethanol and dimethyl ether

6. 4.Metamerism:
❑ Identical molecular formula but different alkyl groups on either side of functional groups.
❑ eg. Ether M.F: C4 H10 O
Methyl propyl ether and diethyl ether
5.Tautomerism:
❑ Identical molecular formula but different position of hydrogen atom.
❑ eg. Ketone and enol M.F: C3 H6 O
Acetone and Prop-1-en-2-ol

7. 6.Ring chain isomerism:
❑ Identical molecular formula but possessing open chain and cyclic
structures.
❑ eg. Alkene and cycloalkane M.F:C3 H6
Prop-1-ene and Cyclopropane

8. ➢ Stereochemistry is the study of three-dimensional structure of molecules.
➢ Stereoisomerism (also known as spatial isomerism) has identical molecular
formula and identical molecular structure but different in spatial arrangement of
atoms. (three dimensional structure).

9. Stereoisomerism
Configurational
Optical
isomerism
Enantiomerism
Diastereoisomerism
Conformational
Geometric
isomerism

10. • Stereoisomers that are produced by rotation about single
bond and are often rapidly interconverted at room
temperature.
• Eg:

11. • Stereoisomers that do not readily interconvert at room
temperature and can be separated.
• Different spatial forms arises out of rotation about C=C.

12. ✓ The compounds which have similar chemical and
physical properties but differ only in their optical
activity are known as optical isomers and phenomenon
as optical isomerism.
OPTICALACTIVITY:
✓ It is the capability of a molecule to rotate the plane
polarized light either towards left or towards right.
✓ Compounds which can rotate plane polarized light is
known as optically active.
✓ Compounds which cannot rotate plane polarized light
is known as optically inactive.
+ and – Lactic acid

13. • Optical activity is measured using
an instrument called Polarimeter.
• A polarimeter allows polarized
light to travel through a sample tube
containing an organic compound and
permits measurement of the degree
to which the light is rotated.

14. • Plane-polarized light arises from passing ordinary light through a
polarizer.

15. ➢A simple polarimeter consists of a
i. Light source- produces light vibrating in all directions
ii. Polarizing lens- filter only allows through light vibrating in one direction
iii. Sample tube - Plane polarised light passes through sample
iv. If substance is optically active it rotates the plane polarised light
v. Analysing lens - filter is turned so that light reaches a maximum
vi. Direction of rotation is measured coming towards the observer.

16. • With achiral compounds, the light that exits the sample tube remains
unchanged. 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 is measured in degrees (°) and is
called the observed rotation. A compound that rotates polarized light
is said to be optically active.

17. Optical rotation:
• The rotation of plane polarized light is measured as angular degree and expressed as observed
rotation (α).
Specific rotation:
• The angle of rotation when plane polarized light is passed through 1 decimeter cell of the
solution having concentration of 1 gram per milliliter.
where α = observed rotation
l = path length of cell (dm) t = temperature
c = concentration of solution (g/ml) λ = wavelength of light
• Specific Rotation depends on the nature of substance, wavelength of light used,
concentration of the solution, thickness of the layer, nature of the solvent and temperature
at which experiment is conducted.

18. Dextrorotatory (+):
• An optically active compound that rotates plane polarized light
in a clockwise direction or towards right.
• Indicated by (+) or (d)
Levorotatory (-):
• An optically active compound that rotates plane polarized light
in a anticlockwise direction or towards left.
• Indicated by (-) 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.

19. • Enantiomers are any pair of stereoisomers that are non-superimposable mirror images
of each other.
• Enantiomers are related to each other like a right hand is related to a left hand.
• Enantiomers are said to be Chiral.

20. Eg: Alanine Lactic acid

21. Tartaric acid Glucose

22. ❖ Enantiomers have identical physical properties (bp, mp, density, solubility and
refractive index) but there is a difference in direction of rotation of plane polarized
light.
❖ They have identical chemical properties except in chemical reactions with other
optically active compounds.

23. ❖ They have different biological properties.
Eg. Thalidomide
❖ When equal quantities of enantiomers are mixed an optically inactive compound
racemic mixture is formed.

24. • Stereoisomers which are not mirror images of one another and
are non superimposable are termed as Diastereomers.
• They have different physical properties like m.p, b.p, solubility,
density and refractive index, etc.
• So it can be separated easily through conventional methods such as
distillation, recrystallisation and chromatography etc.,
• Diastereomers have different specific rotation but they may have
same or opposite sign of rotation.

25. Eg: d-tartaric acid and meso tartaric acid
l-tartaric acid and meso tartaric acid

26. Eg: Pentane-2 ,3-diol

27. ENANTIOMERS DIASTEREOMERS
Mirror images of each other Not mirror images
Non superimposable images of each
pair
Non superimposable image of different
stereoisomers
Identical physical and chemical
properties
Different physical properties and
similar chemical properties
Not easy to separate Easy to separate by physical methods
One or more stereo centres Two or more than two stereo centres

28. ➢A meso compound is a molecule with multiple
stereocenters which is superimposable on its mirror
image.
➢Meso compounds are achiral compounds that has
multiple chiral centers.
➢It has an internal symmetry plane that divides the
compound in half.
➢Internal plane (plane of symmetry) that splits the
compound into two symmetrical sides, the
stereochemistry of both left (-) and right side (+)
should be opposite to each other which balanced total
internal rotation.
➢Therefore, meso compounds becomes optically
inactive.

29. • Eg: 1,2-dichloroethane-1,2- diol

30. • Symmetry is defined as a balanced similarity that is found in two halves
of an object.
• It means one-half is the mirror image of the other half and if it is not
similar then known as Asymmetry.
• Elements of symmetry play a important role in identification of optically
active compounds.
• For a molecule to be optically active, it should be devoid of the following
three elements of symmetry:
1. Plane of symmetry- mirror plane
2. Centre of symmetry- inversion centre
3. Alternating Axis of symmetry- improper rotation of axis

31. ❖ A plane of symmetry is an 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 other side.
❖ It is particularly useful if the molecule contains two or more chiral centres.

32. ❖ Eg:

33. ❖ A centre of symmetry is defined as an imaginary point in a molecule from which
lines drawn on opposite sides at equal distance, meet exactly similar groups or atoms
in the molecules.
❖ Centre of symmetry is possibly present in even-membered ring systems.

34. ❖ Eg: 1,4-dichloro-2,5-dibromobenzene

35. ❖ A molecule is said to possess an n-fold alternating axis 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 original molecule.

36. ❖ Eg: An imaginary molecule 1,2,3,4- tetramethyl cyclobutane.
❖ A and C are similar compounds and thus it contains alternating axis of symmetry.

37. Chiral and achiral molecules
Chiral centre:
➢ A chiral centre is defined as an atom in a molecule
which is bonded to four different atoms or groups.
➢ i.e chiral centre is a tetrahedral atom.
Other terms:
➢ Stereogenic centre
➢ Assymetric centre
➢ Stereocentre

38. Chiral and achiral molecules
• Although everything has a mirror image, mirror images may or may
not be superimposable.
• A molecule which is superimposable on its mirror image is said to be
achiral (lacking chirality).
• A molecule or object that is not superimposable on its mirror image
is said to be chiral.
• Generally, a chiral carbon atom is sp3 with four different
attachments.

39. CHIRAL MOLECULES (chirality)
• Some molecules are like hands. Left and right hands are mirror
images, but they are not identical or not superimposable.

40. CHIRAL MOLECULES
• Eg: 2-butanol
• A and its mirror image labeled B are not superimposable.
• Thus, 2- butanol is a chiral molecule and A and B are isomers.
• Non-superimposable mirror image stereoisomers like A and B are called
enantiomers.

41. ACHIRAL MOLECULES
• In general, a molecule with no chiral centre (stereogenic center) are
achiral.
• Achiral molecules usually contain a plane of symmetry.
• A plane of symmetry is a mirror plane that cuts a molecule in half, so
that one half of the molecule is a reflection (mirror image) of the
other half.

42. • Two identical attachments on an sp3 carbon atom eliminates the
possibility of a chiral center.