Stereochemistry at Tetrahedral Centers

1. Chapter 5 Stereochemistry at Tetrahedral Centers Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

2. Isomers Compounds that have the same molecular formula but different structures.

3. Constitutional Isomers Constitutional isomers differ in the way the atoms are connected. Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

4. Cis–Trans Isomers Cis–trans isomers result from restricted rotation. Cyclic structures restrict rotation. Cis: The substituents are on the same side of the ring. Trans: The substituents are on opposite sides of the ring.

5. Cis–Trans Isomers Double bonds restrict rotation. Cis: The hydrogens are on the same side of the double bond. Trans: The hydrogens are on opposite sides of the double bond.

6. Cis–Trans Isomers Cis–trans isomers have different physical properties. Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

7. Some Alkenes Do Not Have Cis–Trans Isomers

8. Different Conformations Compounds with different conformations (conformers) cannot be separated. Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

9. Different Configurations Compounds with different configurations can be separated. Cis–trans isomers have different configurations.

10. Stereochemistry • Some objects are not the same as their mirror images (technically, they have no plane of symmetry) • A right-hand glove is different from a left-hand glove. The property is commonly called “handedness” • Organic molecules (including many drugs) have handedness that results from substitution patterns on sp3 hybridized carbon

11. Chiral and Achiral Objects Chiral objects – not superimposable on their mirror image Achiral objects – superimposable on their mirror image

12. Chiral Molecules Chiral molecules have an asymmetric center. An asymmetric center is an atom that is attached to four different groups.

13. Compounds with an Asymmetric Center Asymmetric centers are also called chirality centers.

14. Enantiomers The two isomers are called enantiomers. Enantiomers are different compounds: they can be separated. Enantiomers have the same physical and chemical properties.

15. Enantiomers Enantiomers are nonsuperimposable mirror images.

16. Chiral and Achiral Molecules Chiral compounds have nonsuperimposable mirror images. Achiral compounds have superimposable mirror images (they are identical molecules).

17. Asymmetric Center versus Stereocenter Asymmetric center: an atom attached to four different groups Stereocenter: an atom at which the interchange of two groups produces a stereoisomer

18. Examples of Enantiomers • Molecules that have one carbon with 4 different substituents have a nonsuperimposable mirror image – enantiomer • Which of the following are enantiomers?

19. 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 (See Figure 5.4 for examples)

20. Plane of Symmetry

21. Plane of Symmetry • The plane has the same thing on both sides for the flask • There is no mirror plane for a hand

22. Asymmetric (Chirality) Centers inChiral 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

23. Optical Activity • Light restricted to pass through a plane is plane-polarized • Plane-polarized light that passes through solutions of achiral compounds retains its original plane of polarization • Solutions of chiral compounds rotate plane-polarized light and the molecules are said to be optically active Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

24. Plane-Polarized Light

25. An Achiral Compound is Optically Inactive An achiral compound does not rotate the plane of polarization of plane-polarized light.

26. A Chiral Compound is Optically Active A chiral compound rotates the plane of polarization of plane-polarized light. Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

27. Measurement of Optical Rotation • A polarimeter measures the rotation of plane-polarized light that has passed through a solution • The source passes through a polarizer and then is detected at a second polarizer • The angle between the entrance and exit planes is the optical rotation.

28. A Polarimeter • Rotation is measured in degrees, [] • Clockwise rotation is called dextrorotatory = (+) • Counterclockwise rotation is levorotatory = (-) Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

29. Specific Rotation • To have a basis for comparison, we define specific rotation, []D for an optically active compound • []D = observed rotation/(pathlength x concentration) = /(l x C) = degrees/(dm x g/mL) • Specific rotation is that observed for 1 g/mL in solution in cell with a 10 cm path using light from sodium metal vapor (589 nm)

30. 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

31. Pasteur’s Discovery of Enantiomers • Louis Pasteur discovered that sodium ammonium salts of tartaric acid crystallize into right handed and left handed forms • The optical rotations of equal concentrations of these forms have opposite optical rotations • The solutions contain mirror image isomers, called enantiomers and they crystallized in mirror image shapes – such an event is rare

32. How to Draw Enantiomers Perspective formulas Fischer projections

33. Sequence Rules for Specification of Configuration • A general method applies to the configuration at each chirality center (instead of to the whole molecule) • 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 and compared • The relationship of the groups in priority order in space determines the label applied to the configuration, according to a rule

34. Sequence Rules (IUPAC) Rule 1: • Look at the four atoms directly attached to the chirality center, and rank them according to atomic number. • With the lowest priority group pointing away, look at remaining 3 groups in a plane • Clockwise is designated R (from Latin word for “right”) • Counterclockwise is designated S (from Latin word for “left”)

35. Sequence Rules (Continued) Rule 2: • If a decision cannot be reached by ranking the first atoms in the substituents, look at the second, third, or fourth atoms until difference is found

36. Sequence Rules (Continued) Rule 3: • Multiple-bonded atoms are equivalent to the same number of single-bonded atoms

37. Naming Enantiomers Assign relative priorities to the four groups. Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

38. Naming Enantiomers draw an arrow from 1 to 2 to 3 if the lowest priority group is on a hatched wedge, then clockwise = R and counterclockwise = S

39. Naming Enantiomers If the lowest priority group is not on a hatched wedge, switch a pair so it is on a hatched wedge. Then, name the new compound.

40. Naming Enantiomers if the lowest priority group is on a vertical bond, then clockwise = R and counterclockwise = S

41. Naming Enantiomers if the lowest priority group is on a horizontal bond, then counterclockwise = R and clockwise = S

42. R and S Versus (+) and (–) Some R enantiomers are (+) and some are (–). Some S enantiomers are (+) and some are (–). Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

43. If One Enantiomer Is (+), the Other Is (–)

44. Compounds with Two Asymmetric Centers maximum # of stereoisomers = 2n (n = # of asymmetric centers) 1 and 2 are enantiomers. 3 and 4 are enantiomers.

45. Diastereomers 1 and 2 are enantiomers. 3 and 4 are enantiomers. Diastereomers are stereoisomers that are not enantiomers. 1 and 3 are diastereomers. 2 and 3 are diastereomers. 1 and 4 are diastereomers. 2 and 4 are diastereomers. Diastereomers have different physical and chemical properties.

46. Let’s Examine 2-amino-3-hydroxybutanoic acid

47. Two Asymmetric Centers, Four Stereoisomers The cisstereoisomers are a pair of enantiomers. The trans stereoisomers are a pair of enantiomers. Assis. Prof. Dr. Nadhir Najim Abdullah Jafar/ Al-Mustaqbal university college/ Dep. of Pharmacy/ organic chemistry (I)

48. Identifying an Asymmetric Center An asymmetric center is attached to four different groups. two asymmetric centers, four stereoisomers

49. No Asymmetric Centers There are only two stereoisomers: cis and trans.

50. No Asymmetric Centers There are only two stereoisomers: cis and trans.