Organic Chemistry
By
Dr. Mehnaz Kamal
Assistant Professor,
Pharmaceutical Chemistry
Prince Sattam Bin Abdulaziz University
1-Defintion of Isomers.
2-How they could be Classified?
3- Naming of different isomers.
4-Some of their physical and
chemical properties.
Stereochemistry
It is that part of the science which deals with structure in three
dimensions
Study of the arrangement of atoms in space (three-dimensional
shape “3D”) or molecules and how this affects their chemical and
physical properties
Z
Y
2D vs 3D
Y
X
X
Lecture Contents
Isomerism
 Structural Isomerism
1. Chain isomerism
2. Position isomerism
3. Functional isomerism
 Stereoisomerism
1. Optical active isomers.
2. Geometrical isomers.
3. Conformational isomers.
Isomerism
Isomerism
A phenomenon resulting from
moleculs having the same molecular
formula but different arrangement
In space.
When
two
or
more
organic
compounds have the same molecular
formula but differ in their physical or
chemical properties they are called
Isomers and the phenomenon called
isomerism.
Type of Isomerism….cont
1-Structural isomerism /Constitutional isomers.
They are different molecules. They have the same
formula, but they are connected together differently
You cannot convert one to the other without taking it apart and
rebuilding it ( i.e., without breaking and remaking bonds).
All the physical properties of constitutional isomers are different
different melting points and boiling points, different solubility
and densities, etc.
Thy include: A) Chain Isomerism (Or Skeletal Isomerism)
B) Positional Isomerism.
C) Functional Isomerism
Type of Isomerism….cont
1-Structural isomerism /Constitutional isomers..cont
Constitutional isomers include:
A. Chain isomers
CH3
C5H12
CH3
H
C
CH2 CH3
CH2 CH2
CH3
n-pentane
2-methylbutane
CH3
CH2
CH3
Br
C3H7Br
Br
1-bromopropane
C. Functional isomers
H
O
C2H6O
H3C
CH3
Dimethyl ether
H3C
C
CH3
2,2-dimethylpropane
B. Position isomers
2-bromopropane
CH3
CH3
C
H
Ethanol
OH
Type of Isomerism….cont
1-Structural isomerism /Constitutional isomers..cont
Type of Isomerism….cont
1-Structural isomerism /Constitutional isomers..cont
Examples
Write all of the constitutional isomers having the molecular formula
C3H6O2
O
O
O
O
O
O
O
H
H
O
O
OH
CH3
C4H10
CH3CH2CH2CH3
CH3-CH-CH3
CH3
C3H8O
CH3CH2CH2CH2CH3
CH3-CH-CH2CH3
OH
OH
OH
OH
OH
C 6 H6 O2
OH
Catechol
Resorcinol
Hydroquinone
(CH3)4C
Type of Isomerism….cont
2-Stereoisomerism
Greek, Stereos=occupying space).
The stereoisomers have the same structural formulas but differ in
their arrangement of atoms in space but have the same bonding
pattern.
In other words, stereoisomerism is exhibited by such
compounds which have identical molecular structure
but different configurations.
Stereoisomers are the same constitutional isomer, but have a
difference in the way they are arranged in three-dimensional space at
one or more of their atoms.
Type of Isomerism
There are two main
classes of isomers:
Isomers
Structural isomerism
(Constitutional isomers)
Stereoisomerism
Configurational
Position of
function groups
Skeleton or chain
of carbon
Conformational
Functional group
Optical isomers
(Diastereomers
Enantiomers(
Geometrical
Cis & trans
Type of Isomerism….cont
2-Stereoisomerism
Conformational isomers
The atoms at either end of a single bond can rotate relative to one
another.
compare
Free rotation of carbon- carbon
single bonds
Type of Isomerism….cont.
Configuration Isomers
2-Stereoisomerism…cont.
Differ only in arrangement of their atoms in space (3D geometry)
I-Diastereomers (Geometric isomerism)
• Compounds which have the same molecular formula
but differ in arrangement of atoms or groups in space
different configuration
• Diastereoisomers have different physical and chemical
properties, as solubility and boiling points
thus:
- if liquids……. Fractional distillation
- if solids …….. Fractional crystallization
Type of Isomerism….cont.
2-Stereoisomerism…cont.
I-Diastereomers (Geometric isomerism)
An isomerism resulting from rigidity in molecules and occurs
only in two class of compounds
alkenes and cyclic compounds
Rigidity ≠ Flexibility
σ – bond
 - bond
σ – bond
free rotation ( flexibility )
C=C
no free rotation ( rigidity )
restricted rotation ( semi-flexible)
Type of Isomerism….cont.
2-Stereoisomerism…cont.
I-Geometric isomerism…cont
Restricted rotation of carbon-carbon double bonds
Type of Isomerism….cont.
2-Stereoisomerism…cont.
I-Geometric isomerism…cont
i- Geometric isomerism in alkenes
The requirement for this type of isomerism is that each carbon
atom involved in the double bond has different substitution
D
A
C
D≠E
C
A≠B
B
E
Cl
Cl
On same side
cis
H
C
Cl
C
H
C
H
H
C
Cl
On different sides
trans
Geometrical Isomerism
cis/trans isomers
a
b
C
C
c
d
If a ≠ c and b ≠ d then there are 2 diastereomeric forms:
cis, Latin on this side
Cl
Cl
C
H
trans, Latin across
Cl
H
C
C
H
cis-1,2-Dichloroethene
H
C
Cl
trans-1,2-Dichloroethene
COMPARE cis / trans ISOMERS IN RING COMPOUNDS
R
R
C
C
H
C
H
C
R
H
cis
R
H
R
trans
R
R
R
In alkenes cis / trans isomers used to be called geometric isomers,
a term generally not used for cyclic systems (rings). You may find the
term geometric isomers used in older books or papers.
H
Cl
C
H
Cl
Cl
C
C
Cl
1,1-dichloroethene
H
C
Cl
1,1,2-trichloroethene
cis-trans isomerism is not possible if one carbon atom of
the double bond bears 2 identical groups.
Which of the following alkenes can exist as cis-trans isomers?
Draw their structures?
H2C
H3CHC
CHCH2CH3
CHCH3
H2C
C(CH3)2
H3CH2CHC
CHCl
Summary
• Cis-trans isomers differ from one another in the way the
atoms/ groups are positioned in space
– Cis –same, trans –across
– They have different physical and chemical properties
– They interact differently with enzymes/ receptor sites
– They cannot be interconverted by rotation around C-C
bonds
• Rotation is restricted by double bond or cyclic
structure
Type of Isomerism….cont.
2-Stereoisomerism…cont.
I-Geometric isomerism…cont
Diastereoisomers are designed cis or trans according
to the priority order or sequence rule
[ atomic number]
53I
> 35Br > 17Cl > 16S > 9F > 8O > 7N > 6C > 1H
Type of Isomerism….cont.
2-Stereoisomerism…cont.
I-Geometric isomerism…cont
Sequence Rule or Priority Order
1- If the two atoms in question are different, the atom of
highest atomic number receives the highest priority
I > Br > Cl > ……
H
H
C
H2C=HC
H
C
CH2CH2CH3
C
CH3
H 3C
C
OH
trans
cis
H
Br
C
H 3C
C
Cl
cis
2-Stereoisomerism…cont.
I-Geometric isomerism…cont
Sequence Rule or Priority Order
2- If the two atoms are identical, the atomic numbers of next
atoms are used, until the priority is determined at the first
point of difference along the chain
H
H
CH2OH
C
C
C
H3 C
CH2CH2CH3
H3C
CH2NH2
C
CH2CH3
cis
trans
H
CH2CH2CL
C
H 3C
C
CH2CH2Br
trans
2-Stereoisomerism…cont.
I-Geometric isomerism…cont
Sequence Rules or Priority Order
3- Atoms attached to double or triple bonds are given single-bond
equivalencies, each doubly bonded atom is duplicated (or triplicated for triple
bonds)
O
O
R
R-C-R
O
C
N
N
R
R
R-C
O
O
C
N
O
O
N
R
R-C-OH
C
OH
O
O
R-C-OH > R-C-R > R-C-H > RCH2OH >RCN >
>-CH=CR2
E / Z SYSTEM OF NOMENCLATURE
Diastereoisomers can also be designated by:
1- E instead of trans
2- Z instead of cis
cis or trans?
E and Z Based on Priority:
Cahn- Ingold-Prelog:
1. Atomic Number
2. Atomic number of the
next atom
35 2
17Cl 1
Br
---------------53 I C C
1
9F 2
(E)-1-bromo-2-chloro2-fluoro-1-iodoethene
Higher priority at the opposite side of pi bond (E)
Higher priority at the same side of pi bond (Z)
In this system the two groups attached to each carbon
are assigned a priority ( 1 or 2 ).
If priority 1 groups are both on same side of double bond:
Z isomer = zusammen = together (in German)
same
side
1
1
2
2
Z
1
2
2
opposite
sides
1
E
If priority 1 groups on opposite sides of double bond:
E isomer = entgegen = opposite (in German)
ASSIGNING PRIORITIES
1. Look at the atoms attached to each carbon of the double bond.
2. The atom of higher atomic number has higher (1)
priority.
example
1
1
F
F>H
2
H
I
Br
I > Br
2
Since the 1’s are on the same side, this compound is Z
(Z)-1-bromo-2-fluoro-1-iodoethene
notice use of parentheses
ClH2CH 2C
Br
H3C
Cl
c3
4d
 On carbon c, the chloroethyl substituent is of higher priority than
methyl
 On carbon d, the bromine substituent is of higher priority than
chlorine
 IUPAC name is (Z)-1-bromo-1,4-dichloro-2-methylbut-1-ene
O
C
H
CR2
C
N
O
O
CH2OH
H
R
Increasing priority
H2N
CO2H
Cl
Br
Z
H2N
Br
Cl
CO2H
E
OH
CO2H
H
H
CO2H
E
Z
cis/trans Geometry of Alicyclic Compounds
The cyclic systems use the traditional cis/trans nomenclature.
trans-1,2-dimethylcyclobutane
cis-1,2-dimethylcyclobutane
trans-1,2-dimethylcyclohexane
cis-1,2-dimethylcyclohexane
Sequence Rules or Priority Order
Examples
H
CHO
C
COOH
O
O
Cis
Z
H 3C
OCH3
CN
cis
O
CCH2Cl
C
C
C
H3CC
H3CC
C
COOH
C
cis
cis
ClH2C
CH2NH2
C
C
H 3C
H2C=HC
H
Cl
C
C
ClH2C
CCH2Cl
Cl
O
Trans
E
Useful resources
http://www.chemeddl.org/resources/stereochem/definitions1.htm
http://orgchem.chem.uconn.edu/courses/243f97-rspractice.html