1. William Brown Thomas Poon www.wiley.com/college/brown Chapter Six Chirality: The Handedness of Molecules

2. 6-2 Isomers In this chapter, we concentrate on enantiomers and diastereomers.

3. 6-3 Enantiomers Enantiomers: Nonsuperposable mirror images As an example of a molecule that exists as a pair of enantiomers, consider 2-butanol.

4. 6-4 Enantiomers One way to see that the mirror image of 2-butanol is not superposable on the original is to rotate the mirror image.

5. 6-5 Enantiomers Now try to fit one molecule on top of the other so that all groups and bonds match exactly. The original and mirror image are not superposable. They are different molecules with different properties. They are enantiomers (nonsuperposable mirror images).

6. 6-6 Enantiomers Objects that are not superposable on their mirror images are chiral (from the Greek: cheir, hand) They show handedness. The most common cause of enantiomerism in organic molecules is the presence of a carbon with four different groups bonded to it. A carbon with four different groups bonded to it is called a stereocenter.

7. 6-7 Enantiomers If an object and its mirror image are superposable, they are identical and there is no possibility of enantiomerism. We say that such an object is achiral (without chirality). As an example of an achiral molecule, consider 2- propanol. Notice that this molecule has no stereocenter.

8. 6-8 Enantiomers To see the relationship between the original and its mirror image, rotate the mirror image by 120°. When we do this rotation, all atoms and bonds of the mirror image fit exactly on the original. This means that the original and its mirror image are the same molecule. They are just viewed from different perspectives.

9. 6-9 Enantiomers To summarize An object that is nonsuperposable on its mirror image is chiral (it shows handedness). The most common cause of chirality among organic molecules is the presence of a carbon with four different groups bonded to it. We call a carbon with four different groups bonded to it a stereocenter. An object that is superposable on its mirror image is achiral (without chirality). Nonsuperposable mirror images are called enantiomers. Enantiomers, like gloves, always come in pairs.

10. 6-10 Drawing Enantiomers Following are four different representations for one of the enantiomers of 2-butanol. Both (1) and (2) show all four groups bonded to the stereocenter and show the tetrahedral geometry. (3) is a more abbreviated line-angle formula; although we show the H here, we do not normally show them in line- angle formulas. (4) is the most abbreviated representation; you must remember that there is an H present on the stereocenter.

11. 6-11 Drawing Mirror Images On the left is one enantiomer of 2-butanol. On the right are two representations for its mirror image (in this case, its enantiomer).

12. 6-12 Naming Enantiomers - R,S Because enantiomers are different compounds, each must have a different name. Here are the enantiomers of the over-the-counter drug ibuprofen. The R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other.

13. 6-13 The R,S System To assign an R or S configuration: Assign a priority from 1 (highest) to 4 (lowest) to each group on the stereocenter; for priority rules, see Section 4.3C. Orient the stereocenter so that the group of lowest priority is facing away from you. Read the three groups projecting toward you in order from (1) to (3). If reading the groups is clockwise, the configuration is R (Latin, rectus, straight, correct). If reading the groups is counterclockwise, the configuration is S (Latin: sinister, left).

14. 6-14 The R,S System Problem: Assign an R or S configuration to each stereocenter.

15. 6-15 The R,S System ProblemProblem: Assign an R or S configuration to the enantiomers of ibuprofen. Remember to add the H at the stereocenter.

16. 6-16 Enantiomers & Diastereomers For a molecule with 1 stereocenter, 2 1 = 2 stereoisomers are possible. For a molecule with 2 stereocenters, a maximum of 2 2 = 4 stereoisomers are possible. nFor a molecule with n stereocenters, a maximum of 2 n stereoisomers are possible.

17. 6-17 Enantiomers & Diastereomers 2,3,4-Trihydroxybutanal Two stereocenters; 2 2 = 4 stereoisomers are possible.

18. 6-18 Meso Compounds Meso compound: an achiral compound possessing two or more stereocenters. Tartaric acid contains two stereocenters. Two stereocenters; 2 n = 4, but only three stereoisomers exist, one meso compound and one pair of enantiomers.

19. 6-19 Cyclic Molecules 2-Methylcyclopentanol 2 stereocenters; according to the 2 n rule, a maximum of 4 stereoisomers are possible. How many actually exist? Answer 4, two pairs of enantiomers.

20. 6-20 Cyclic Molecules 1,2-Cyclopentanediol 2 stereocenters = a maximum of 4 stereoisomers. How many exist? Answer: three, one meso compound (the cis isomer) and one pair of enantiomers (the trans isomer).

21. 6-21 Cyclic Molecules 4-Methylcyclohexanol How many stereoisomers are possible? Answer: two. The cis isomer (achiral) and the trans isomer (also achiral).

22. 6-22 Cyclic Molecules 3-Methylcyclohexanol 2 stereocenters = a maximum of 4 stereoisomers How many exist? Answer: four, two pairs of enantiomers.

23. 6-23 Cyclic Molecules 2-Methylcyclohexanol 2 stereocenters = a maximum of 4 stereoisomers how many exist? Answer: four, two pairs of enantiomers.

24. 6-24 Cyclic Molecules 1,3-Cyclohexanediol 2 stereocenters = a maximum of 4 stereoisomers How many exist? Answer: three, the cis isomer (meso) and the trans isomer (a pair of enantiomers).

25. 6-25 Three Or More Stereocenters How many stereocenters are present in the molecule on the left? How many stereoisomers are possible? One of the possible stereoisomers is menthol. Assign an R or S configuration to each stereocenter in menthol.

26. 6-26 Three Or More Stereocenters Cholesterol On the left is the carbon skeleton of cholesterol. How many stereocenters are present? How many stereoisomers are possible?

27. 6-27 Optical Activity Ordinary light: Light waves vibrating in all planes perpendicular to its direction of propagation. Plane-polarized light:Plane-polarized light: Light waves vibrating only in parallel planes. Polarimeter: An instrument for measuring the ability of a compound to rotate the plane of plane-polarized light. Optically active: Showing that a compound rotates the plane of plane-polarized light.

28. 6-28 Polarimeter Figure 6.6 Schematic diagram of a polarimeter.

29. 6-29 Optical Activity Dextrorotatory: Clockwise rotation of the plane of plane- polarized light. Levorotatory: Counterclockwise rotation of the plane of plane-polarized light. Specific rotation: The observed rotation of an optically active substance at a concentration of 1 g/100 mL in a sample tube 10 cm long; for a pure liquid, concentration is in g/mL (density).

30. 6-30 Chirality in the Biological World Except for inorganic salts and a few low-molecular- weight organic substances, the molecules in living systems, both plant and animal, are chiral. Although these molecules can exist as a number of stereoisomers, almost invariably only one stereoisomer is found in nature. Instances do occur in which more than one stereoisomer is found, but these rarely exist together in the same biological system. It’s a chiral world!

31. 6-31 Chirality in Biomolecules Enzymes (protein bio-catalysts) all have many stereocenters. An example is chymotrypsin, an enzyme in the intestines of animals that catalyzes the digestion of proteins. Chymotrypsin has 251 stereocenters. The maximum number of stereoisomers possible is 2 251 ! Only one of these stereoisomers is produced and used by any given organism. Because enzymes are chiral substances, most either produce or react with only substances that match their stereochemical requirements.

32. 6-32 Chirality in the Biological World Figure 6.7 Schematic diagram of the surface of an enzyme capable of distinguishing between enantiomers.

33. 6-33 Chirality in Biomolecules Because interactions between molecules in living systems take place in a chiral environment, a molecule and its enantiomer or one of its diastereomers elicit different physiological responses. As we have seen, (S)-ibuprofen is active as a pain and fever reliever, whereas its R enantiomer is inactive. The S enantiomer of naproxen is the active pain reliever, whereas its R enantiomer is a liver toxin!

34. 6-34 Resolution Racemic mixture: An equimolar mixture of two enantiomers. Because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero. Resolution: The separation of a racemic mixture into its enantiomers.

35. 6-35 Resolution Enzymes as resolving agents.

36. 6-36 Chirality and the Handedness of Molecules End Chapter 6