1. Pharmaceutical ORGANIC CHEMISTRY
Stereochemistry
Pharmaceutical ORGANIC CHEMISTRY

2. Stereochemistry is the study of molecules on space
i.e. how atoms or groups in a molecule
arranged in space relative to each other
it is that part of the science which deals with structure in three dimensions
is the field of chemistry that concerned with isomerism in space
( stereoisomerism )

3. Lecture contents Isomerism Structural Isomerism Stereoisomerism
1. Chain isomerism
2. Position isomerism
3. Functional isomerism
Stereoisomerism
Optical active isomers.
Geometrical isomers.
Conformational isomers.

4. Isomerism Isomerism (stereoisomerism )
A phenomenon resulting from molecules 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.

5. Stereoisomerism Greek, Stereos=occupying space).
The stereoisomers have the same structural formulas but differ in the spatial arrangement of atoms or groups in the molecule.
In other words, stereoisomerism is exhibited by such compounds which have identical molecular structure but different configurations.

6. 2- Geometrical – The resulting isomerism are known as
Stereochemistry
Type of Isomerism
1- Structural – The resulting isomerism are known as
Structural isomers
2- Geometrical – The resulting isomerism are known as
Diastereoisomers
3- Optical – The resulting isomerism are known as
Enantiomers

7. Isomers
They are compounds that contain the same atoms bonded together in different ways they include:-
1. Constitutional (Structural) isomers.
2. Stereoisomers.
Chain

8. Isomers Isomerism Constitutional Stereoisomers. (Structural) isomers
Chain
isomerism
Optical
isomerism
Chain
Positional
isomerism
Geometrical
isomerism
Functional
isomerism

9. Constitutional Isomers
They differ in the way their atom are connected.
1. Chain isomerism
2. Position isomerism
3. Functional isomerism

10. Chain Isomerism (or Skeletal Isomerism)
Chain isomers have the same molecular formula but differ in order in which the carbon atoms are bonded.

11. Predict
C4H10
C5H12

12. Position Isomerism
Position isomers have the same molecular formula but differ in the position of functional group on the carbon chain.
Examples are:-

13. Predict
C6H6O2
C3H8O

14. Functional Isomerism
Functional isomers have the same molecular formula but different functional groups. Examples are;

15. An isomerism resulting from rigidity in molecules
Stereochemistry
Geometric isomerism
An isomerism resulting from rigidity in molecules
and accures only in two class of compounds
alkenes and cyclic compounds
Rigidity ≠ Flexibility
σ – bond free rotation ( flexibility )
 - bond C = C no free rotation ( rigidity )
σ – bond restricted rotation ( semi-fexable )

16. Free rotation' of carbon- carbon single bonds 
Restricted rotation' of carbon-carbon double bonds 

17. 1- Geometric isomerism in alkenes
Stereochemistry
1- 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 ≠ E
A ≠ B
On same side
cis
On differ side
trans

18. 1- Geometric isomerism in alkenes
Stereochemistry
1- Geometric isomerism in alkenes
Diastereoisomers are designed cis or trans according to
the priority orders or sequence rules
[ atomic number = atomic weight \ 2 ]
126I > 80Br > 35Cl > 32S > 19F > 16O > 14N > 12C > 1H

19. Sequence Rules or Priority Order
Stereochemistry
Sequence Rules 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 > ……

20. Sequence Rules or Priority Order
Stereochemistry
Sequence Rules 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
points of difference along the chain

21. Sequence Rules or Priority Order
Stereochemistry
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 )
>
>
>
>
>
>
RCH2OH
RCN
-CH=CR2

22. Sequence Rules or Priority Order
Stereochemistry
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 )

23. Sequence Rules or Priority Order
Stereochemistry
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 )
Diastereoisomer

24. Stereochemistry E , Z – system of nomenclature
Diastereoisomers can also be designted by :
1- E instead of trans
2- Z instead of cis

25. Stereochemistry Stereochemistry
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 are liquids……. Fractional distillation
- if are solids …….. Fractional crystallization

26. 2- Geometric isomerism in cyclic compounds
Stereochemistry
2- Geometric isomerism in cyclic compounds
The most illustrative example is cyclohexane
Rotation of group ( atoms ) around sigma bonds,
result in different conformations ( conformer )

27. 2- Geometric isomerism in cyclic compounds
Stereochemistry
2- Geometric isomerism in cyclic compounds
All cyclic compounds except cyclopentane would be
strained because ……

28. 2- Geometric isomerism in cyclic compounds
Stereochemistry
2- Geometric isomerism in cyclic compounds
Conformation is different arrangement ….
In ethane
Newman projection
Ball and stick
3D formula

29. 2- Geometric isomerism in cyclic compounds
Stereochemistry
2- Geometric isomerism in cyclic compounds
Cyclohexane is not flat ….
Axial hydrogen ( Ha ) : H parallel to axis
Equatorial hydrogen ( He ) : H in plane
upon flipping and reflipping between conformers, axial becomes
equatorial and equatorial becomes axial

30. 2- Geometric isomerism in cyclic compounds
Stereochemistry
2- Geometric isomerism in cyclic compounds
Mono-substituted cyclic compounds, do not exhibit
geometrical ………
cis or trans

31. 2- Geometric isomerism in cyclic compounds
Stereochemistry
2- Geometric isomerism in cyclic compounds
1,2-disubstituted : same as 1,4-disubstituted
Cis
both down = e,a
both up = a,e
Trans
up and down = a,a
down and up = e,e
1,4-disubistuted cyclohexane as 1,2
In summary : a,e e,a
a,a e,e

32. 2- Geometric isomerism in cyclic compounds
Stereochemistry
2- Geometric isomerism in cyclic compounds
1,3-disubstituted :
both down = e,e
both up = a,a
up and down = a,e
down and up = e,a

33. Label each of the following disubistiuted rings as
cis or trans and as a,a ; e,e ; or a,e