Pharmaceutical Organic

Chemistry

Topic: Stereochemistry &

stereoisomers

Handout-3
 Stereochemistry
 The Arrangement of Atoms in Space or
three dimensional structure of atoms.

 Isomers are compounds that have the

same molecular formula but with different
structures.

 There are two main classes of isomers:

1-Structural isomers (or constitutional
isomers)
2-Stereo-isomers
 Isomers

constitutional
stereoisomers
isomers

Optical isomers Diastereomers:

or Enantiomers Configurational &
Cis-trans diastereomers
 I-Constitutional isomers:
These are compounds whose atoms are connected
differently .
Different connections among atoms which may be due
to difference in:
A- Skeleton of carbon or
B- Functional groups or
C- Position of functional groups
 II-Stereoisomers:
These are compounds whose atoms are
connected in the same order but with
different geometry or arrangements.

Types of Stereoisomers are:

A- Geometric isomers or Cis &trans isomers or

cis &trans stereomers (both in alkenes and
cycloalkanes)
B- Optical isomers (e.g. enantiomers &
configurational diastereomers)
 GEOMETRIC ISOMERISM

CH3 H CH3 CH3

C C C C

H CH3 H H
trans but-2-ene cis but-2-ene
(E) but-2-ene (Z) but-2-ene

BOTH C ATOMS OF C=C MUST HAVE

TWO DIFFERENT GROUPS

© www.chemsheets.co.uk A2 011 12-Jul-12

 Geometric isomers
Which type of molecule can give Geometrical isomerism?

There are two requirements for Geometrical

isomerism.
• There must be double bond between two carbon
(means rotation must be restricted in the molecule)
• There must be two different (non-identical) groups
on each doubly bonded carbon atom.

Geometrical isomers can be either cis or trans

isomers
 How to identify cis-trans isomers?
•Give priority (big group) to groups at both carbon
by checking the atomic no. of connected atoms.
•If highest priority group on both carbon is on
same side called Cis or Z and if opposite called
Trans or E.

So above compound is Cis or Z isomers because Highest

priority group on the same side.
 Why is the boiling point of the cis isomers higher?

melting point
isomer boiling point (°C)
(°C)

cis-but-2-ene -139 4
•There must be stronger intermolecular forces between
trans-but-2-ene
the -106 than between 1trans
molecules of the cis isomers
isomers.
•Taking 1,2-dichloroethene as an example:

•Cis-1,2-dichloroethene
Why is the boiling point of the cis isomers higher? Answer
•Because of this, there will be dipole-dipole
interactions as well as dispersion forces - needing
extra energy to break. That will raise the boiling
point.
Why is the melting point of the cis isomers lower?
•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.
 Exercise-1
CH3 CH3 H CH3
C C C C
H CH2 CH3 CH3 CH2 CH3
Trans (E) Cis (Z) YES
3-Methylpent-2-ene Geometrical
Isomerism
H H

C C
NO
H CH2 CH3 Geometrical Isomerism

But-1-ene
 Exercise-2
CH3 CH3 CH3 CH2 CH3

C C C C YES

CH3 CH2 CH2 CH3 CH3 CH2 CH3

Cis (Z) Trans (E)

3,4-dimethylhex-3-ene

CH3 CH3 CH3 Cl

YES
C C C C

Br Z Cl Br E CH3
2-bromo-3-chlorobut-2-ene
 Home Work
CH3 H

C C NO

CH3 H
methylpropene

H H H Cl

C C C C YES

Z E
CH3 Cl CH3 H
1-chloropropene
 Home Work
CH3 CH2 CH3

C C NO

CH3 H
2-methylpent-2-ene

H CH2 CH2 CH3

C C NO

H CH2 CH3
2-ethylpent-1-ene
 Optical Isomerism
Optical activity and structure of
compounds
 The chiral carbon atom

a carbon atom with four

different groups attached to it
w

x C y also called:
chiral center; chiral carbon
z asymmetric center
asymmetric carbon
stereocenter
stereogenic center
 Optical activity and structure of
compounds
Chiral carbon atoms
4 different substituents on carbon, then it is no longer
superimposable on its mirror image and we say that carbon is chiral .

CO2 CO2

H
H
H3C CH3
NH2 H2N

L (-) alanine D (+) alanine

• A molecule is chiral if two mirror image forms are not superimposable
upon one another.
• A molecule is achiral if its two mirror image forms are superimosable

• In above picture chair iwill be achiral as its mirror image is

superimposable.The chiral centre is usually indicated by an asterisk (*)
• A molecule with a single chiral carbon must be chiral
• But, a molecule with two or more chiral carbons may be chiral or
may be not.
 Bromochlorofluoromethane is chiral

It cannot be
Cl superimposed
Br
H

F
 Chirality and chiral carbons

A molecule with a single stereogenic center is chiral.

2-Butanol is an example.

CH3 C CH2CH3

OH
Examples of molecules with 1 chiral carbon

CH3

CH3CH2CH2 C CH2CH2CH2CH3

CH2CH3

one chiral alkane

Examples of molecules with 1 chiral carbon

OH

Linalool, a naturally occurring chiral alcohol

Examples of molecules with 1 chiral carbon

H2C CHCH3

O
1,2-Epoxypropane: a chiral carbon
can be part of a ring
attached to the chiral carbon are:
—H
—CH3
—OCH2
—CH2O
 PREFIXES USED TO DENOTE
CHIRAL PROPERTIES
PREFIX PROPERTY
d-/l- Rightward (dextro), clockwise/Leftward
(leuvlo), counterclockwise, optical rotation.
Used interchangably with (+)/(-)
D-/L- Rightward/leftward arrangement of
substituents about chiral center (archaic,
used for amino acids & carbohydrates)
R-/S- Rightward (rectus)/leftward (sinister) arrange-
ment of substituents about chiral center
(modern, used for drugs)

e.g., R-(-)- levorotatory, but with absolute configuration R

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 Assignning Absolute Configuration
(R) & (S) Configuration
(Cahn-Ingold-Prelog R/S system)
In the R,S system, groups are assigned priority using the Cahn-
Ingold-Prelog system just as in the E,Z system for naming
alkenes.
To assign (R) or (S) configuration to a chiral carbon:
1. Rank the 4 atoms (groups) attached to the carbon .
2. Project the molecule so that the group (atom) of lowest priority is to
the rear.
The most probable atoms used are:
H=1, C=6, N=7, O=8, F=9, S=16, Cl=17, Br=35
Br> Cl> S> F>O >N> C> H
3. Select the group (atom) of highest priority and draw a curved arrow
toward the group (atom) of next lowest priority. (assign priority in
order of decreasing atomic number).
4. Clockwise orientation (arrow direction) is R or dextro. Counterclockwise
arrow direction is S or levo.
 For Practice: Identify d or l form
2-hydroxypropanoic acid (lactic acid)

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2-aminopropanoic acid (alanine)
This is typical of naturally-occurring amino acids.
Structurally, it is just like the last example, except that the
-OH group is replaced by -NH2

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 Conformational Isomers of Alkanes

Conformations are different arrangements of atoms that

are interconverted by rotation about single bonds.

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Conformational Isomers can be-
•Eclipsed conformation, the C—H bonds on one carbon are
directly aligned or parallel with the C—H bonds on the
adjacent carbon.
•Staggered conformation, the C—H bonds on one carbon
bisect (divide into equal half) the H—C—H bond angle on the
adjacent carbon.

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• Rotating the atoms on one carbon by 60° converts an
eclipsed conformation into a staggered conformation, and
vice versa.
• The angle that separates a bond on one Carbon atom from a
bond on an adjacent Carbon atom is called a dihedral angle.
• For ethane in the staggered conformation, the dihedral angle
for the C—H bonds is 60°. For eclipsed ethane, it is 0°.

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 How to Draw a Newman Projection:
Conformations are commonly drawn using a convention called
a Newman projection.
Step 1. Look directly down the C—C bond (end-on), and draw a circle
with a dot in the center to represent the carbons of the C—C bond.

Step 2. Draw in the bonds.

Draw the bonds on the front C as three lines
meeting at the center of the circle.
Draw the bonds on the back C as three lines
coming out of the edge of the circle.
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 Newman projections for
the staggered and eclipsed conformations of ethane

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 Newman projections for
the staggered and eclipsed conformations
1-chloropropane

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 HOME WORK

Draw Newmans Projection for

1-chloropropane between C-2 and C-3

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THE END

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