1. University of Nizwa Oman
Dr. Ghulam Abbas
Assistant Professor
University of Nizwa

2. Stereochemistry
The foundations of organic stereochemistry were laid by Jacobus van’t Hoff and Joseph Achille Le Bel in 1874.
The Greek word stereos means “solid,” and
stereochemistry refers to chemistry in three dimensions. Isomers that have the same constitution but differ in the spatial arrangement of their atoms are called stereoisomers.
In 1894, William Thomson (Lord Kelvin) defined an object as chiral if it is not superimposable on its mirror image.

3. The work “chiral” is derived from the Greek word cheir,
meaning “hand,” and it is entirely appropriate to speak of
the “handedness” of molecules.
The opposite of chiral is Achiral. A molecule that is superposable on its mirror image is achiral.
Stereoisomers that are related as an object and its
nonsuperposable mirror image are classified as
enantiomers.
An example is bromochlorofluoromethane
(BrClFCH).

6. Definitions
Stereoisomers – compounds with the same connectivity, different arrangement in space
Enantiomers – stereoisomers that are non- superimposible mirror images; only properties that differ are direction (+ or -) of optical rotation
Diastereomers – stereoisomers that are not mirror images; different compounds with different physical properties

7. Definitions
Asymmetric center – sp3 carbon with 4 different groups attached
Optical activity – the ability to rotate the plane of plane –polarized light
Chiral compound – a compound that is optically active (achiral compound will not rotate light)
Polarimeter – device that measures the optical rotation of the chiral compound

8. STEREO ISOMERISM
Stereo isomers are the compounds whose atoms are connected in same order but differ from one another only in (spatial arrangement) the arrangement of atoms in three-dimensional space.
It is due to the free rotation around the carbon-carbon single bonds in open chain molecule. This process is called stereo isomerism and the compounds are said to stereo isomers of each other.

9. STEREO ISOMERS ARE OF TWO TYPES. Configurational Isomerism
Conformational Isomerism
Configurational Isomerism
The isomerism in which two compounds are inter converted only by the breaking and making of bonds such compounds are called Configurational Isomerism. H C H 3 H h v H C H R 3 o t a t i o n H H C H 3 H C H C H 3 3 C H 3

10. Cis/Trans Isomerism:
When disubstituted (two substituents other than hydrogen) alkenes contain two substituents on the same side of the double bond they are called cis alkenes and when substituents are attached to opposite side are called trans alkenes.
Two methyl groups on the same side of double bond = Cis

11. E and Z Alkenes
For trisubstituted (three substituents) and tetrasubstituted (four substituents) double bonds, a more general method is needed for describing double-bond geometry.
If the Higher mass ranked groups are on the same side, then alkene has Z geometry (German zusammen, meaning “together.”) If the higher-ranked groups are on opposite sides, while the alkene has E geometry (German entgegen, meaning “opposite).

12. Examples: (Z)-3-methyl-2-pentene or (3-methyl-cis-2-pentene
(E)-1-bromo-1-chloropropene

13. Conformational Isomerism
The stereo isomerism in which two compounds are inter converted to one another only by the rotation of bonds around the C-C single bond. Thus the two compounds are called conformational isomers/Conformers.
Example: In ethane due the free rotation of bonds around a single bond different arrangement of ethane is possible as shown.
These different arrangement of atoms caused by free rotation around a single bond are called conformation and specific structure is called conformer

14. Conformational isomers
Conformational isomers are represented in two ways;
Sawhorse representation: It shows molecules at an angle, showing a molecular model. C-C bonds are at an angle to the edge of the page.
Newman projections: Bonds to front carbon are lines going to the center while bonds to back/rear carbon are lines going to the edge of the circle as shown;

15. Conformational isomers
Experiments show that there is a small (12 kJ/mol or 2.9 kcal/mol) barrier to rotation and that some conformations are more stable than others.
The lowest energy, most stable conformation is the one in which all six C - H bonds are as far away from one another as possible called staggered conformation when viewed end-on in a Newman projection. The highest-energy, least stable conformation is the one in which the six C -H bonds are as close as possible called eclipsed in a Newman projection.

16. Conformational isomers
Conformational situation is more complex for larger alkanes.
Not all staggered conformations have same energy, and not all eclipsed conformations have same energy. In butane, the lowest-energy arrangement, called the anti conformation, is the one in which the two methyl groups are as far apart as possible—180° away from each other.

17. Chirality The word chirality refers to the property of “handnesss”
Your right and left hands are very similar, yet they are not identical.
They are related to each other as mirror images and as such they can’t be superimposed on top of each other . Molecule can also be chiral if they contain one or more chiral centers.

18. Prochiral
A molecule is said to be prochiral if it can be converted from achiral to chiral in a single chemical step. For instance, an unsymmetrical ketone like 2-butanone is prochiral because it can be converted to the chiral alcohol 2-butanol by addition of hydrogen.
+ H2

19. Enantiomeric Relationship
They have the same solubility, physical, and
spectroscopic properties and the same chemical reactivity toward achiral reagents.
Enantiomers differ in a specific physical
property, namely the rotation of plane polarized light.
The property of rotating plane polarized light is called optical activity

20. Enantiomers Configurational isomers are in turn comprised of
Enantiomers and Diastereoisomers.
Enantiomers
The non super imposable mirror images of a compounds is called enantiomers (d or l rotatory) they are are optically active because they cane rotate the plane of polarized either to right or to left. Example: 3, 4 Dibromobutane.

21. 2, 3 Dibromobutane
Lactic Acid

22. Not superimposable isomers

23. Cahn-Ingold-Prelog (CIP) System OR
R and S Configuration (Absolute Configuration)

24. Cahn-Ingold-Prelog System

25. R and S Configurations

26. R and S Configuration
Examples S = = S c) R

27. Tartaric Acid: Used by Pasteur
Examples
Meso Compound

28. Chiral Centre (stereogenic Centre)
The carbon atom having four different atoms and can not be subdivided in to two equal halves.

29. Optical Isomerism
The compounds having the same molecular formulas, structural formulas, physical and chemical properties but differing in their action on plane polarized light are called optical isomer and phenomenon is called optical isomerism.
Optical activity
The property of a compound to rotate the plane polarized light in either direction is called optical activity. OR
The substance rotating the plane of polarized to the left or right is called optical active and this property of rotating planner polarized light is called optical activity.

30. Plane polarized light
The light oscillating in single plane is called plane-polarized light. If we observed the beam of light of ordinary light from one end, we will find that oscillation of electric field and magnetic fields are occurring in all possible planes perpendicular to the directions of propagations.
When ordinary light is passed through a polarizer, it loses its horizontal components. The resulting ray is oscillating in single plane.

31. Dextro rotatory ( or d form)
Laevo Rotatory (or l form)
The molecule rotating the plane of polarized light to the left is called Laevo rotatory or l form.
Dextro rotatory ( or d form)
The molecule rotating the plane of polarized light to the right is called dextro rotatory or d form.

32. DIASTERIOISOMER
Those stereo isomer which are not mirror images of one another are known as diasterioisomers. Or
They are the stereoisomerisms which must have opposite (mirror image) configuration at one or more chiral centers but the same configurations at another chiral canters.

33. Examples Vants Hoff Rule
For a molecule with multiple chiral centers, the number of possible diastereoisomers is given by the equation X = 2n
Where X is the number of possible isomers and n is the number of stereogenic centers.

34. Other Examples of Diastereoisomer is 2-chloro-2 Butanol

35. The relation between structure (i), (iii), (iv) is known as diastereoisomers, Structure (i), (ii) are enatiomers and they must have identical properties, the same true for structure (iii) and (iv).
How ever the properties of Structure (i) and (ii) are not identical with those of structure (iii) and (iv). They have different melting points, Boiling points and solubility reactivity and all other properties.

36. The Relationship between Chirality and Symmetry
a) Not have plane of symmetry
b) Not have center of symmetry
What kinds of molecules display optical activity:
For example, trans, trans, cis-2,4-dichloro-1,3
Dimethyl cyclobutane has a center of symmetry,
but no plane of symmetry. It is achiral.

37. MESO COMPOUND
A compound whose molecules are superimposable on their mirror images, even though they contain chiral centers. It is optically inactive. (They have plane of symmetry).

39. Chiral compounds in organic chemistry
1) Compounds with a chiral carbon atoms.
2) Compounds with other Quadrivalent chiral atoms.
3) Compounds with Trivalent chiral atoms.
4) Suitably substituted adamantens.
5) Restricted rotation giving rise to perpendicular
dissymmetric planes.
6) Chirality due to a helical shape.
7) Chirality caused by restricted rotation of other type.

40. 1) Compounds with a chiral carbon atoms.
2) Compounds with other tetravalent chiral atoms.

41. 3) Compounds with Trivalent chiral atoms.
Umbrella effect = Pyramidal inversion is Achiral. However; It becomes chiral in following cases;
1) Nitrogen atoms in a three-member ring.
2) Nitrogen atoms connected to another atom bearing an unshared electron pair.
3) Nitrogen atoms in bridgehead bicycle systems.

42. Sulfonium salts, sulfoxides, and phosphines can be obtained as pure enantiomers, Because there is a relatively high energy barrier to inversion of these tetrahedral molecules.

43. 4) Restricted rotation giving rise to perpendicular dissymmetric planes (Atropisomers).
a) 1 1’-biphenyl compounds: Steric interactions between the ortho hydrogens prevent these molecules from being planar.

45. D and L Configuration (Relative Configuration)
Fischer Convention (D and L description) for the configuration of carbohydrates and natural substances.
Two enantiomers of glyceraldehyde were originally arbitrarily assigned the configuration D and L. This assignment was then confirmed by X-Ray crystallography.

47. Monoosaccharide

48. Epimer