1. 1 ISOMERISM

2. 2 Contents Isomers-Definitions Geometrical isomers Nomenclature for Geometrical isomers Optical Isomerism Nomenclature For Optical Isomers Racemic Mixtures

3. 3 Isomers Same molecular formula with different structural formula is called Isomers & phenomenon is called as Isomerism. Example-(C 3 H 8 O) n propanol Methyl ethyl ether

4. 4 Types Of Isomers Stereoisomer Geometrical Isomers Optical Isomers

5. Geometrical Isomers Introduction: Geometrical isomers occur as a result of restricted rotation about a carbon-carbon bond. Single bond between two carbons in a non cyclic structure may rotate around each other at room temperature because as the carbons rotate around each other the degree of overlap between 5

6. the atomic orbitals is not changed and remain at maximum overlap as rotation occurs. 6

7. Reason: If there is a double bond between two carbons, these sp2 carbons have a sigma overlap or bond between two sp2 hybrid orbitals and a Pi overlap as a result of the p overlap.The sigma overlap would not change its maximum overlap as a result of rotation about the two sp2 carbons. However if the two sp2 carbons attempt to rotate about each other this will reduce the p-p overlap of the Pi bond. The Pi bond prevents the carbons from rotating about each other. 7

8. If the similar groups are fixed on the same side as a result of this restricted rotation, then the isomer would be classified as “cis”. The similar groups are fixed due to restricted rotation by double bond on opposite side of the double bond then this isomer is “trans”. The cis and trans isomers are differ in their physical and chemical properties. 8

9. cis-trans isomers 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 9

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11. e.g 11

12. E and Z nomenclature rule The E/Z system is based on an assignment of priorities to the atoms or groups attached to each carbon of the double bond  If the higher-priority atoms or groups are on opposite sides of the pi bond, the isomer is (E)  If the higher-priority groups are on the same side, the isomer is (Z) 12

13.  The atom with the higher atomic number is of higher priority.  If two atoms are identical, the atomic numbers of the next atoms are used to assign the priority. Priority is determined at the first point of difference along the chain if the atoms have the same atoms directly attached. 13

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15. On carbon 1, the methyl substituent is of higher priority than H On carbon 2, the bromine substituent is of higher priority than H  IUPAC name is (E)-1-bromopropene On carbon 3, the chloroethyl substituent is of higher priority than methyl On carbon 4, the bromine substituent is of higher priority than chlorine  IUPAC name is (Z)-1-bromo-1,4-dichloro-2- methylbut-1-ene 15

16. 16 Stereoisomers Optical Isomers Same molecular formula - same bond connectivities - different arrangement of their atoms in space non-superimposable mirror images W C X Z Y W C X Y Z (also called Enantiomers )

17. 17 Optical Activity Stereoisomers are said to be optically active if the rotate plane polarized light. Each type of enantiomer rotates light the same amount, but in different directions. Amount and direction of rotation must be experimentally determined using a polarimeter. polarimeter

18. 18 Plane polarized light Light that has been passed through a nicol prism or other polarizing medium so that all of the vibrations are in the same plane. non-polarizedpolarized

19. 19 Polarimeter - an instrument used to measure optical activity. light sourcesample tube polarizer analyzer

20. 20 Chirality Chirality Chiral and Achiral Molecules Although everything has a mirror image, mirror images may or may not be superimposable. Some molecules are like hands. Left and right hands are mirror images, but they are not identical, or superimposable.

21. 21 Chiral: A molecule or object that is not superimposable on its mirror image is said to be chiral. Achiral: A molecule or object that is superimposable on its mirror image is said to be achiral. Chirality

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23. 23 Cont… Chiral Centre : A carbon that is bonded to four different groups of atoms. 2-chlorobutane *

24. 24 Enantiomers The enantiomers of lactic acid drawn in two different representations

25. 25 Enantiomers 3-Chlorocyclohexene

26. 26 A nitrogen chiral center Enantiomers

27. Diastereomers Not mirror images.

28. 28 Nomenclature Dextrorotatory – when the plane of polarized light is rotated in a clockwise direction when viewed through a polarimeter. (+) or (d) Levorotatory – when the plane of polarized light is rotated in a counter-clockwise direction when viewed through a polarimeter. (-) or (l) 1.D & L Nomenclature

29. 29 2. R,S Nomenclature Priority rules 1. Each atom bonded to the chiral center is assigned a priority based on atomic number; the higher the atomic number, the higher the priority 2. If priority cannot be assigned per the atoms bonded to the chiral center, look to the next set of atoms; priority is assigned at the first point of difference

30. 30 R,S Nomenclature 3. Atoms participating in a double or triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds.

31. 31 Naming Chiral Centers 1. Locate the chiral center, identify its four substituents, and assign priority from 1 (highest) to 4 (lowest) to each substituent. 2. Orient the molecule so that the group of lowest priority (4) is directed away from you. 3. Read the three groups projecting toward you in order from highest (1) to lowest priority (3). R S. 4. If the groups are read clockwise, the configuration is R ; if they are read counterclockwise, the configuration is S.

32. 32 (S)-2-Chlorobutane Naming Chiral Centers

33. 33 Naming Chiral Centers  (R)-3-Chlorocyclohexene  (R)-Mevalonic acid

34. 34 Racemic mixture an equimolar mixture of two enantiomers because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific rotation is zero. i.e. it is optically inactive.

35. 35 S-thalidomide (effective drug) R-thalidomide (dangerous drug) Racemic mixture of Racemic mixture of Thalidomide

36. 36 Racemic mixture Equal amounts of (+) and (-) enantiomers - rotation is 0 Net rotation is zero.

37. 37 References   Stereochemistry of carbon compounds by Ernest L Eliel   Stereochemistry of Organic Compounds, Principles and Applications, by D. Nasipuri   Stereochemistry Conformation and Mechanism by P.S. Kalsi   Organic Chemistry, Sixth Edition, by Robert Thornton Morrison, Robert Neilson Boyd   www. google.com

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