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 Configuration
Examples S = = S c) R

26. Tartaric Acid: Used by Pasteur
Examples
Meso Compound

27. In Fischer projections the molecule is oriented so that the vertical bonds at the stereogenic center are directed away from you and the horizontal bonds point toward you. A projection of the bonds onto the page is a cross.

28. Manipulation of Fischer Projections
Fischer projections can be rotated by 180° only!
a 90° rotation inverts the stereochemistry and is illegal!
If one group of a Fischer projection is held steady, the other
three groups can be rotated clockwise or counterclockwise. 28 28

29. 29 29

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

31. 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.

32. Optical Activity - molecules enriched in an enantiomer will
rotate plane polarized light are said to be optically active. The
optical rotation is dependent upon the substance, the
concentration, the path length through the sample, and the
wavelength of light.
Polarimeter
589 nm -
D-line of
a sodium
lamp
Plane polarized light: light that oscillates in only one plane 32 32

33. Polarimeter Polarimeter before after
Concentration: pure liquid in g/mL; solution in g per 100 mL of solvent

34. 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.

36. Example Mixture of 30% R and 70% S enantiomer.
The pure R enantiomer has a specific rotation of -40 degrees.
What is the specific rotation of the mixture?
Contribution from S
Contribution from R

37. Specific Rotation
The angle of rotation of monochromatic light that passes through 10cm of the substance in solution at a concentration of 1 gram per mL.
Specific rotation[α], is a fundamental property of chiral substances that is expressed as the angle to which the material causes polarized light to rotate at a particular temperature, wavelength, and concentration.
The term for specific rotation is given by
where T is the temperature, λ is the wavelength of light employed (normally the sodium D-line, or 589 nm), α is the observed rotation, l is the path length, and c is the concentration in grams per milliliter (for pure substances the density) or grams per 100 mL. The solvent (often ethanol, methanol, DSMO, acetone, water, etc.) is also specified. Specific rotation may also be expressed as degrees per mole of the substance.

38. Specific Rotation []D : a standardized value for the optical rotation
= optical rotation in degrees
l = path length in dm
c = concentration of sample in g/100 mL
T = temperature in °C
= wavelength of light, usually D for the
D-line of a sodium lamp (589 nm)
100 
[] = T
l • c
The specific rotation is a physical constant of a chiral molecule
The []D may also depend upon solvent, therefore the solvent is
usually specified.
for alanine:
[]D = +14.5° (c 10, 6N HCl) 20 38 38

39. Example 1: A sample of pure (S)-2-butanol was placed in a 10
Example 1: A sample of pure (S)-2-butanol was placed in a 10.0 cm polarimeter tube.  Using the D line of a sodium lamp, the observed rotation at 20oC was α = +104o.  The density of this compound is g ml-1.  What is the specific rotation of (S)-2-butanol?
Solution: Plugging the numbers into
[α]lT = α/lc
we get: [α]lT = (+104o) / (1.00 dm) (0.805 g ml-1) = +129o.  Thus we would write [α]D20 = +129o (neat). ("Neat" refers to a liquid that has not been diluted.)  

40. Example 2: Calculate the observed rotation of a solution of 0
Example 2: Calculate the observed rotation of a solution of g of (S)-1-amino-1-phenylethane diluted to a volume of 10.0 mL with methanol at 20oC, using the D line of a sodium lamp and a 1.00 dm tube.  Specific rotation of this material: [α]D23 = -30.0o.
Solution: Solving the specific rotation equation for observed rotation, we get
α = [α]lTlc. 
The sample size is g, but this has been diluted to 10.0 mL, so the sample concentration is g in 100 ml.  Plugging in the numbers, we get α = (-30.0o) (1.00 dm) (5.245 g in 100 ml).  Solving, we find α = -157o.

41. : angle (# of degrees) plane polarized light is rotated by an
optically active sample. Expressed in degrees.
Enantiomers will rotate plane polarized light the same magnitude
() but in opposite directions (+ or -)
90% (+) % (-) will rotate light 80% of pure (+)
75% (+) % (-) will rotate light 50% of pure (+)
50% (+) % (-) will be optically inactive
50:50 mixture of enantiomers (+/-): racemate or racemic mixture
Each individual molecule is chiral, however the bulk property
of the substance is achiral, if it is in an achiral environment. 41 41

42. 7.7: Fischer Projections - representation of a three-dimensional
molecule as a flat structure. A tetrahedral carbon is represented
by two crossed lines:
horizontal line is coming
out of the plane of the
page (toward you)
vertical line is going back
behind the plane of the
paper (away from you)
substituent
carbon
(R)-lactic acid
(S)-lactic acid 42 42

43. 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.

44. 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.

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

46. 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.

47. 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.

48. 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).

50. meso tartaric acid: The groups on the top carbon reflect (through the
symmetry plane) onto the groups on
the bottom carbon 50

51. 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.

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

53. 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.

54. 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.

55. 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.

57. Resolution of Enantiomers
Resolution mean resolving the racemic mixture in to pure enantiomers. It a reverse of racemization. There are many ways for the separation of pure enantiomer.
Differential Absorption
When a racemic mixture is placed on a chromatographic column if the column consists of Optically active substances then the enantiomer should move down the column at different rate and they can be easily separated. This can also be done with paper chromatography.

58. Physical Or Mechanical Separation
Pasture grew the crystals of ammonium salt of tartaric acid. He separated the racemic mixture with the help of tweezer. Under the microscope and got two pure enantiomer.
This was a first physical separation of a racemic mixture. But is a tedious and time-consuming method. Secondly it is only limited to those racemic mixtures which are solid and have fine crystals.

59. Biological separation
In the living system enzymes, which controls all the reaction occurring in the living body, are very specific. For example in the human body there are enzyme which are specific for D. glucose (occur in all fruit) and is able to metabolize it).
If a person takes a mixture of D. glucose and L. glucose then enzyme will consume the D. glucose and L. glucose will be secreted out as pure enantiomer. It is very perfect method of separation of racemic mixture but the disadvantage of this method is that we can get only one pure enantiomer.

60. Biochemical process
Certain Bacteria’s and mould of chiral nature when grown in dilute solution of racemic mixture destroy one enantiomer then other. For example Penicillium glaucum when grown in racemic mixture of ammonium tartarte the solution slowly become leveo rotatory (-) because the mould destroy the (+) enantiomer.
Chemical Method
A racemic mixture of two pure enantiomer is not possible to separate because they have same physical properties and chemical properties. However properties of diasteroisomer are quite different from individual isomer and therefore the mixture of diasteroisomer can be separated by fractional distillation.

61. D and L 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.

63. Monoosaccharide

64. Epimer

65. THE END