PHARMACEUTICAL
ORGANIC CHEMISTRY
LEC 2
QI: Arrange the following sets in order of
decreasing priority
-H, -C2H5, -CH3, -C(CH3)3, -CH(CH3)2
Problem 1:
Lecture contents
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Geometrical Isomerism
Optical Isomerism
Polarimeter
Chirality
Chiral compounds
Optical
Isomerism
Stereochemistry
Optical isomerism
An isomerism resulting from ability of certain molecules
to rotate plane of polarized light
-- the light is rotated either to the right or left
right ( clockwise )
left ( anticlockwise )
+
-
d ( dexter ) dextro
l ( laevous ) levo
 Polarimetry is a laboratory technique that measures
the interaction between a compound and plane
polarized light.
 Since enantiomers interact with plane polarized light
differently, polarimetry can be used to distinquish
between enantiomers.
Optical Isomerism:
 Any
material that rotates the plane of polarized
light is said to be optically active.
 Optically active compound is nonsuperimposable on its
mirror image.
 If a molecule is superimposable on its mirror image, the
compound does not rotate the plane polarized light; it is
optically inactive.
 Example:
CH3
- Alanine
(amino acid)
H2N
C
H
COOH
 Enantiomers are different compounds:
 Same boiling point, melting point, density
 Rotate plane polarized light in opposite directions
(polarimetry)
 Different interaction with other chiral molecules
 Enzymes
 Receptor
CHIRALITY
AND
CHIRAL
COMPOUNDS
What is chirality?
 Chirality (cheir, Greek for hand).
 The property of nonsuperimposability of an
object on its mirror image is called chirality.
 If a molecule is not superimposable on its
mirror image, it is chiral. If it is
superimposable on its mirror image, it is
achiral.
Chirality
• Carbons with four different groups attached to them
are handed, or chiral.
• Optical isomers or stereoisomers
• If one stereoisomer is “right-handed,” its enantiomer is
“left-handed.”
CHIRAL COMPOUNDS
 Compounds which contain chiral carbon.
 Chiral carbon:
 It is an sp3-hybridized carbon atom with
four different groups attached to it.
 Chiral compound exists in a pair of
enantiomers.
Chirality
S-ibuprofen
• Many pharmaceuticals are chiral.
• Often only one enantiomer is clinically active.
 Enantiomers have identical physical
and chemical properties except in two
important respects:
1. They rotate the plane polarized light in
opposite directions, however in equal
amounts.
 The isomer that rotates the plane to the left
(anticlockwise) is called the levo isomer and
is designated (-)
 While the one that rotates the plane to the
right (clockwise) is called the dextro isomer
and designated (+).
2. They react at different rates with other chiral
compounds.
 This is the reason that many
compounds are biologically
active while their enantiomers
are not.
 They react at the same rates with
achiral compounds.
Stereochemistry
Optical isomerism
Determination of Number of Enantiomers
[stereoisomers]
2n
where n = number of chiral carbins
n = zero
1
2
3
4
5
no possible stereoisomers
2 enantiomers are possible
4~ ~ ~ ~ ~ ~ ~
8~ ~ ~ ~ ~
~
16 ~ ~ ~ ~ ~ ~
32 ~ ~ ~ ~ ~ ~
Summary
Stereoisomers: isomers that have same formula
and connectivity but differ in the position of the
atoms in space. They possess one or more
stereocenters.
Stereocenter: a carbon atom bearing 4 different
atoms or group of atoms.
Chiral: any molecule that is nonsuperposable
with its mirror image.
Enantiomers: stereoisomers that are non
superposable mirror images.
Optically Active: the ability of some
compounds to rotate plane polarized light.
TASK
1)
2)
3)
4)
Which of the following molecules are optically
active?
propan-2-ol
2-chlorobutane
1-chlorobutane
3-methylhexane
5)
6)
7)
8)
butanone
2-methylbutanoic acid
butan-2-ol
1-chloro-3-methylpentane