1. بسم الله الرحمن الرحیم امام جواد ( ع ): اظهار کار پیش از استحکام ، باعث خرابی است.

2. OPTICAL ACTIVITY PLANE-POLARIZED LIGHT

3. . PLANE-POLARIZED LIGHT BEAM unpolarized beam wavelength = c frequency ( ) c = speed of light polarized beam All sine waves (rays) in the beam aligned in same plane. Sine waves are not aligned in the same plane. NOT PLANE-POLARIZED END VIEW SIDE VIEW single ray or photon A beam is a collection of these rays.

4. Optically Active Refers to molecules that interact with plane-polarized light Jean Baptiste Biot French Physicist - 1815 He discovered that some natural substances (glucose, nicotine, sucrose) rotate the plane of plane-polarized light and that others did not.

5. Optical Activity incident polarized light transmitted light (rotated) sample cell angle of rotation,  (usually quartz) a solution of the substance to be examined is placed inside the cell 

6. Dextrorotatory Rotates the plane of plane-polarized light to the right. (+)- d-d- Levorotatory Rotates the plane of plane-polarized light to the left. (-)- l-l- TYPES OF OPTICAL ACTIVITY newolder newolder

7. [  ] D =  cl Specific Rotation [  ] D  = observed rotation c = concentration ( g/mL ) l = length of cell ( dm ) D = yellow light from sodium lamp t = temperature ( Celsius ) t Specific rotation calculated in this way is a physical property of an optically active substance. This equation corrects for differences in cell length and concentration. You always get the same []D[]D t value of

8. SPECIFIC ROTATIONS OF BIOACTIVE COMPOUNDS cholesterol-31.5 cocaine-16 morphine-132 codeine-136 heroin-107 epinephrine-5.0 progesterone+172 testosterone+109 sucrose+66.5  -D-glucose+18.7  -D-glucose+112 oxacillin+201 COMPOUND []D[]D[]D[]D

9. The Polarimeter chemistry nerd sample cell polarizer Na lamp plane is rotated analyzer  plane-polarized light observed rotation 0 0 0 0 0 rotate to null

10. STEREOISOMERS ENANTIOMERS

11. PASTEUR’S DISCOVERY Louis Pasteur 1848 Sorbonne, Paris + + 2- tartaric acidsodium ammonium tartrate ( found in wine must ) Pasteur crystallized this substance on a cold day.

12. (+) (-)(-) Louis Pasteur separated these and gave them to Biot to measure. Biot’s results : mirror images Crystals of Sodium Ammonium Tartrate hemihedral faces Pasteur found two different crystals.

13. Enantiomers W C X Z Y W C X Y Z non-superimposable mirror images Pasteur decided that the molecules that made the crystals, just as the crystals themselves, must be mirror images. Each crystal must contain a single type of enantiomer. (also called optical isomers)

14. Pasteur’s hypothesis eventually led to the discovery that tetravalent carbon atoms are tetrahedral. Only tetrahedral geometry can lead to mirror image molecules: Square planar, square pyrimidal or trigonal pyramid will not work: tetrahedral carbon Van’t Hoff and LeBel (1874)

15. ENANTIOMERS HAVE EQUAL AND OPPOSITE ROTATIONS W C X Z Y W C X Y Z (+)-nn o (-)-nn o dextrorotatorylevorotatory Enantiomers ALL OTHER PHYSICAL PROPERTIES ARE THE SAME

16. (as a minor component) ALSO FOUND more about this compound later (+)-tartaric acid(-)-tartaric acid TARTARIC ACID from fermentation of wine [  ] D = 0 meso -tartaric acid Enantiomers

17. TARTARIC ACID (-) - tartaric acid(+) - tartaric acid [  ] D = -12.0 o [  ] D = +12.0 o mp 168 - 170 o solubility of 1 g 0.75 mL H 2 O 1.7 mL methanol 250 mL ether insoluble CHCl 3 solubility of 1 g 0.75 mL H 2 O 1.7 mL methanol 250 mL ether insoluble CHCl 3 d = 1.758 g/mL meso - tartaric acid mp 140 o d = 1.666 g/mL solubility of 1 g 0.94 mL H 2 O [  ] D = 0 o insoluble CHCl 3

18. RACEMIC MIXTURE an equimolar (50/50) mixture of enantiomers [  ] D = 0 o the effect of each molecule is cancelled out by its enantiomer

19. CHIRALITY, SYMMETRY PLANES AND ENANTIOMERS AND ENANTIOMERS

20. WHICH OBJECTS ARE SYMMETRIC ? (mirror image is identical) sym asym sym (outside) asym sym asym sym

21. asym sym asym sym asym (due to pattern) WHICH OBJECTS ARE SYMMETRIC? ( continued )

22. PLANES OF SYMMETRY

23. plane of symmetry mirror plane A SYMMETRIC OBJECT HAS A PLANE OF SYMMETRY - ALSO CALLED A MIRROR PLANE - ALSO CALLED A MIRROR PLANE

24. IF AN OBJECT HAS A PLANE OF SYMMETRY, ITS MIRROR IMAGE WILL BE IDENTICAL SUPERIMPOSE IDENTICAL MIRROR IMAGES WILL SUPERIMPOSE (MATCH EXACTLY WHEN PLACED ON TOP OF EACH OTHER)

25. CHIRALITY

26. no symmetry CHIRAL An object without symmetry is The mirror image of a chiral object is different and will not superimpose on the original object. OBJECTS WHICH ARE CHIRAL HAVE A SENSE OF “HANDEDNESS” AND EXIST IN TWO FORMS

27. ACHIRAL An object with symmetry is ACHIRAL ( not chiral). The mirror image of an achiral object is identical and will superimpose on the original object. plane of symmetry

28. The whole secret of the study of nature lies in learning how to use ones eye. George Sand, author

29. ENANTIOMERS STEREOISOMERS

30. ENANTIOMERS non-superimposable mirror images rotate this molecule is chiral note that the fluorine and bromine have been interchanged in the enantiomer do interchanges in class

31. STEREOISOMERS ENANTIOMERS are a type of STEREOISOMER 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. and remember …...

32. STEREOGENIC CARBON ATOMS

33. STEREOCENTERS One of the ways a molecule can be chiral is to have a stereocenter. A stereocenter is an atom, or a group of atoms, that can potentially cause a molecule to be chiral. stereocenters - can give rise to chirality

34. STEREOGENIC CARBONS A stereogenic carbon is tetrahedral and has four different groups attached. stereocenter This is one type of …. …. others are possible ( called “chiral carbons” in older literature ) H F Cl Br

35. ACHIRAL TWO IDENTICAL GROUPS RENDERS A TETRAHEDRAL CARBON ACHIRAL The plane of the paper is a plane of symmetry F Cl Br

36. ONE PAIR OF ATOMS ATTACHED TO A TETRAHEDRAL CARBON IS IN A PLANE PERPENDICULAR TO THE OTHER PAIR Look at your model set ! plane 1 plane 2 F Cl Br

37. Cl Cl Br F F Br ClCl plane of symmetry TWO VIEWS OF THE PLANE OF SYMMETRY side view edge view F Cl Br

38. A CARBON ATOM WITH THREE SIMILAR GROUPS IS ALSO ACHIRAL ….. ACHIRAL Cl Br

39. Cl Cl Br Br ClCl plane of symmetry side viewedge view Cl Cl

40. CONFIGURATION The three dimensional arrangement of the groups attached to an atom Stereoisomers differ in the configuration at one or more of their atoms.

41. DETERMINATION OF DETERMINATION OF R / S CONFIGURATION R / S CONFIGURATION IN FISCHER PROJECTIONS

42. 2 CONFIGURATION CONFIGURATION - relates to the three dimensional sense of attachment for groups attached to a chiral atom or group of atoms (i.e., attached to a stereocenter). clockwise counter clockwise (rectus)(sinister) view with substituent of lowest priority in back 1 2 4 3 C C 1 4 3 RS

43. CONFIGURATION Enantiomers are assigned a CONFIGURATION using the same priority rules we developed for E/Z stereoisomers. 1. Higher atomic number has higher priority. 2. If priority cannot be decided based on the first atom attached move to the next atom, following the path having the highest prioity atom. 3. Expand multiple bonds by replicating the atoms attached to each end of the bond. SPECIFICATION OF CONFIGURATION SEQUENCE RULE CAHN-INGOLD-PRELOG

44. 1 2 3 4 RS Bromochlorofluoroiodomethane 1 3 2 4 Enantiomers

45. H CH 2 OH CHO OH PLACE THE PRIORITY=4 GROUP IN ONE OF THE VERTICAL POSITIONS, THEN LOOK AT THE OTHER THREE H OH OHC CH 2 OH 1 2 3 4 1 2 3 4 R alternatively: H CH 2 OH CHO OH 1 2 3 4 HOCH 2 CHO OH 2 1 4 3 H R #4 at top position#4 at bottom position BOTH IN BACK SAME RESULT

46. H CH 2 OH CHO OH 1 2 3 4 FOR THE MENTALLY AGILE WHY BOTHER INTERCHANGING? JUST REVERSE YOUR RESULT! H coming toward you Same molecule as on previous slide. S reverse R Same result as before.

47. CH 2 OH CH 2 OH H CHO OH 1 2 3 4 H CH 2 OH 1 2 3 4 HO CYCLIC ROTATION OF GROUPS IN A FISCHER PROJECTION FISCHER PROJECTION YOU MAY FIX ONE GROUP AND THEN ROTATE THE OTHER THREE H CHO OH 1 3 4 2 Any of the four groups may be fixed. This rotation does not change the molecule. R configuration fixed rotate

48. NUMBER OF NUMBER OF STEREOISOMERS POSSIBLE

49. How Many Stereoisomers Are Possible? maximum number of stereoisomers = 2 n, where n = number of stereocenters (sterogenic carbons) sometimes fewer than this number will exist

50. * * 2 2 = 4 stereoisomers R R S S R S * * * 2 3 = 8 stereoisomers R R R R R S R S R S R R R S S S R S S S R S S S

51. TYPES OF ISOMERS

52. CONSTITUTIONAL ISOMERS Isomers with a different order of attachment of the atoms in their molecules STEREOISOMERS Isomers with the same order of attachment, but a different configuration (3D arrangement) of groups on one or more of the atoms ISOMERS Different compounds with the same molecular formula cis/trans ISOMERS ENANTIOMERS Stereoisomers whose molecules are non- superimposible mirror images of each other DIASTEREOMERS Stereoisomers whose molecules are not mirror images of each other each isomer could double bond or ring both can apply have stereoisomers with a ring TYPES OF ISOMERISM (geometric)

53. MOLECULES WITH MOLECULES WITH TWO STEREOCENTERS DIASTEREOMERS / MESO

54. 2 2 = 4 stereoisomers possible ** 1234 2-Bromo-3-chlorobutane SR RS SS RR When comparing butanes, the comparisons are done best using the eclipsed conformation. The relationships and planes of symmetry are not easily seen in other conformations.

55. H CH 3 H ClBr CH 3 HH CH 3 CH 3 ClBr 1 2 3 4 HH CH 3 CH 3 ClBr 1 2 3 4 PRIORITIES AND DETERMINING R and S reversed

56. enantiomers 1 enantiomers 2 diastereomers SR RS SS RR mirror 2-Bromo-3-chlorobutane

57. enantiomers-1 enantiomers-2 diastereomers Models of the Isomers of 2-Bromo-3-chlorobutane Br Cl CH 3 H (methyl groups are reduced to a single red atom)

58. ** 2,3-Dichlorobutane Now there is the possibility of a plane of symmetry. The existence of a plane reduces the number of stereoisomers that are possible. You will not find all 2 n (= 4) stereoisomers. CC Cl HH CH 3 ( Replace the Bromine with a second Chlorine ) (2 n = 4)

59. meso enantiomers diastereomers SR S S RR mirror image is identical 2,3-Dichlorobutane

60. HH CH 3 CH 3 ClCl H CH 3 Cl H CH 3 Cl plane of symmetry MESO ISOMER SR mirror Meso isomer - has a plane of symmetry and the mirror image is identical to the original molecule.

61. meso diastereomers enantiomers Cl CH 3 H Models of the Isomers of 2,3-Dichlorobutane (methyl groups are reduced to a single red atom)

62. CONCLUSION When a molecule has 1. multiple stereocenters and 2. there is a possibility of an arrangement with a plane of symmetry you will not always find all of the 2 n stereoisomers that are possible. Some of the stereoisomers may be meso isomers, and their mirror images will be superimposable (identical) - this will eliminate at least one of the possible stereoisomers, and sometimes more. 2 n = the maximum number

63. PHYSICAL PROPERTIES OF PHYSICAL PROPERTIES OF ENANTIOMERS, DIASTEREOMERS AND MESO COMPOUNDS AND MESO COMPOUNDS

64. ENANTIOMERS HAVE EQUAL AND OPPOSITE ROTATIONS W C X Z Y W C X Y Z (+)-nn o (-)-nn o dextrorotatorylevorotatory Enantiomers ALL OTHER PHYSICAL PROPERTIES ARE THE SAME REMEMBER :

65. IN CONTRAST : DIASTEREOMERS MAY HAVE DIFFERENT ROTATIONS AND ALSO DIFFERENT PHYSICAL PROPERTIES

66. FISCHER PROJECTIONS

67. CHO HOCH 2 H OH OHH CHO CH 2 OH H CH 2 OH CHO OH EVOLUTION OF THE FISCHER PROJECTION Substituents will stick out toward you like prongs Fischer Projection Main chain bends away from you “Sawhorse” Projection Orient the main chain vertically with the most oxidized group at the top.

68. ORIENTATION OF THE MAIN CHAIN AND THE SUBSTITUENTS IN A FISCHER PROJECTION continuation of the main chain OH H H H

69. INCREASING OXIDATION STATE increasing oxidation state In the Fisher projection the main chain is oriented with the most highly oxidized group at the top. C=O on carbon-2 increases the priority of C-OH

70. HH CH 3 CH 3 ClBr CH 3 H H Cl Br main chain in red orient main chain vertically convert to Fischer Projection rotate 90 o Br Cl CH 3 H H

71. Mirror images (enantiomers) are created by switching substituents to the other side. This is equivalent to turning the molecule over like a pancake. OPERATIONS WITH FISCHER PROJECTIONS All stereocenters must be switched to get an enantiomer (the mirror inverts them all). diastereomers enantiomers If you switch only some of the stereocenters, not all of them, you get a diastereomer.

72. Rotation by 180 o in the plane of the paper does not change the molecule. No other angle of rotation is allowed. 180 o OPERATIONS WITH FISCHER PROJECTIONS. Rotation can be used for comparisons …..

73. 3 A Does A have an enantiomer A* ? CH 3 Br Br CH CH 1) reflect A* 3 Br Br CH 3 HC 2) rotate 3 Br Br CH 3 3) compare NO !

74. A The molecule did not have an enantiomer because it was not chiral. It had a plane of symmetry, rendering it a meso molecule. THE MOLECULE WAS MESO ! plane of symmetry

75. OTHER EXAMPLES

76. diastereomers 3- Chloro-2-butanol enantiomers-1enantiomers-2

77. 2,3-Dichlorobutane meso diastereomers enantiomers