فصل ششم : شیمی فضائی

1. فصل ششم : شیمی فضائی فصل ششمشیمی فضائی نور قطبیده نور غیر قطبیده نور غیر قطبیده نور قطبیده

2. 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.

3. a a 0 0 0 0 0 polarizer analyzer The Polarimeter observed rotation plane-polarized light Na lamp sample cell plane is rotated chemist rotate to null

4. فصل ششم : شیمی فضائی ایزومرهای ساختمانی نحوه اتصال اتمها متفاوت است ایزومرهای هندسی وضع هندسی اتمها متفاوت است

5. Stereochemistry Some objects are not the same as their mirror images (they have no plane of symmetry) A right-hand glove is different than a left-hand glove The property is commonly called “handedness” Many organic molecules (including most biochemical compounds) have handedness that results from substitution patterns on sp3 hybridized carbon 5

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

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

8. Enantiomers non-superimposable mirror images (also called optical isomers) W W C C Y X X Y Z Z 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.

9. CHIRAL An object without symmetry is no symmetry 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

10. The flask has a mirror plane, or plane of symmetry There is no mirror plane for a hand 10

11. 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

12. Enantiomers – Mirror Images

13. H F Cl Br STEREOGENIC CARBONS ( called “chiral carbons” in older literature ) stereocenter A stereogenic carbon is tetrahedral and has four different groups attached.

14. C l C l C l C l B r C l B r C l plane of symmetry side view edge view

15. Chirality Centers A point in a molecule where four different groups (or atoms) are attached to carbon is called a chirality center There are two nonsuperimposable ways that 4 different groups (or atoms) can be attached to one carbon atom A chiral molecule usually has at least one chirality center 15

16. Enantiomers and the Tetrahedral Carbon • Enantiomers are molecules that are not the same as their mirror image • They are the “same” if the positions of the atoms can coincide on a one-to-one basis (we test if they are superimposable, which is imaginary) • This is illustrated by enantiomers of lactic acid

17. Mirror-image Forms of Lactic Acid When H and OH substituents match up, COOHand CH3don’t when COOH and CH3coincide, Hand OH don’t 17

18. Examples of Enantiomers • Molecules that have one carbon with 4 different substituents have a nonsuperimposable mirror image – enantiomer

19. Les énantiomères ont les mêmes propriétés physiques et chimiques, exceptées les réactions où la chiralité entre en jeu, ce qui est le cas dans les mécanismes biologiques. Un exemple tristement célèbre est celui de la thalidomide [1], un sédatif utilisé dans les années 60. A cette époque, un laboratoire avait commercialisé une formulation où figurait un mélange des deux énantiomères du principe actif (pour des questions de coût). Or si un des énantiomères était effectivement un sédatif, l'autre était un tératogène. De nombreuses femmes enceintes ont fait les frais de cette découverte, et les industries pharmaceutiques prennent désormais de sérieuses précautions pour éviter de renouveler cette erreur, en cherchant systématiquement à comparer l'activité biologique de deux énantiomères

20. thalidomide

21. The Reason for Handedness: Chirality Molecules that are not superimposable with their mirror images are chiral (have handedness) A plane of symmetry divides an entire molecule into two pieces that are exact mirror images A molecule with a plane of symmetry is the same as its mirror image and is said to be achiral 21

22. Plane of symmetry A plane of symmetry bisects a molecule into two mirror image halves. Chlorodifluoromethane has a plane of symmetry.

23. Plane of symmetry Aplane of symmetry bisects a molecule into two mirror image halves.1-Bromo-1-chloro-2-fluoroethene has a planeof symmetry.

24. Mirror Planes of Symmetry • If two groups are the same, carbon is achiral. • A molecule with an internal mirror plane cannot be chiral.* Caution! If there is no plane of symmetry, molecule may be chiral or achiral. See if mirror image can be superimposed.

25. cis-1,2-dichlorocyclopentane trans -1,2-dichlorocyclopentane 25

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

28. Chirality Centers in Chiral Molecules • Groups are considered “different” if there is any structural variation (if the groups could not be superimposed if detached, they are different) • In cyclic molecules, we compare by following in each direction in a ring

29. R R R S S R S S R R R R R S R S R S R R R S S S R S S S R S S S * * 22 = 4 stereoisomers * * * 23 = 8 stereoisomers

32. Problem: Chirality Centers?

33. Center of symmetry A point in the center of themolecule is a center of symmetry if a line drawn from it to any element, when extended an equal distance in the opposite direction, encounters an identical element.

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

35. (R), (S) Nomenclature • Different molecules (enantiomers) must have different names. • Usually only one enantiomer will be biologically active. • Configuration around the chiral carbon is specified with (R) and (S).

36. Specific Rotation and Molecules • Characteristic property of a compound that is optically active – the compound must be chiral • The specific rotation of the enantiomer is equal in magnitude but opposite in sign (or direction).

37. Sequence Rules for Specification of Configuration • The configuration is specified by the relative positions of all the groups with respect to each other at the chirality center • The groups are ranked in an established priority sequence (the same as the one used to determine E or Z)and compared. • The relationship of the groups in priority order in space determines the label applied to the configuration, according to a rule

38. (R), (S) Nomenclature • Different molecules (enantiomers) must have different names. • Usually only one enantiomer will be biologically active. • Configuration around the chiral carbon is specified with (R) and (S).

39. Cahn-Ingold-Prelog Rules • Assign a priority number to each group attached to the chiral carbon. • Atom with highest atomic number assigned the highest priority #1. • In case of ties, look at the next atoms along the chain. • Double and triple bonds are treated like bonds to duplicate atoms.

40. فصل ششم : شیمی فضائی قواعد توالی برای تعیین آرایش فضائی : 1. اتمهای که مستقیما به مرکز کایرال متصل هستند را بر حسب کاهش وزن اتمی مرتب کنید . 2. اگر اولویت و تقدم گروهها را با استفاده از قاعده اول نتوانستید تعیین کنید در این صورت از دومین اتم در گروهها استفاده کنید و اولویت گروهها را تعیین کنید. 3. اتمی که با پیوند چند گانه به اتم دیگر اتصال دارد به عنوان چند اتم که با پیوند های ساده به اتم دیگر اتصال دارد تلقی می شود. R S R S

41. Sequence Rules (IUPAC) • Assign each group priority according to the Cahn-Ingold-Prelog scheme With the lowest priority group pointing away, look at remaining 3 groups in a plane • Clockwise is designated R (from “Rectus” Latin for “right”) • Counterclockwise is designated S (from “Sinister” Latin word for “left”)

42. Assign (R) or (S) • Working in 3D, rotate molecule so that lowest priority group is in back. • Draw an arrow from highest to lowest priority group. • Clockwise = (R), Counterclockwise = (S)

43. R-Configuration at Chirality Center • Lowest priority group is pointed away and direction of higher 3 is clockwise, or right turn

44. expands to 4 Assign Priorities 2 4 3 3 4 1 2 1 3 1 2

45. Examples of Applying Sequence Rules • If lowest priority is back, clockwise is R and counterclockwise is S

46. Practice Problem

47. Problem: Assign R or S

48. Problem: R or S?

49. Problem: Same structure or Enantiomers?

50. Properties of Enantiomers • Same boiling point, melting point, density • Same refractive index • Different direction of rotation in polarimeter • Different interaction with other chiral molecules • Enzymes • Taste buds, scent