1. 15 15-1 © 2003 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 7e Bettelheim, Brown, and March

2. 15 15-2 © 2003 Thomson Learning, Inc. All rights reserved Chapter 15 Chirality - the Handedness of Molecules Chirality - the Handedness of Molecules

3. 15 15-3 © 2003 Thomson Learning, Inc. All rights reserved Isomers Types of isomers in this chapter we study enantiomers and diastereomers

4. 15 15-4 © 2003 Thomson Learning, Inc. All rights reserved Enantiomers Enantiomers: Enantiomers: nonsuperposable mirror images as an example of a molecule that exists as a pair of enantiomers, consider 2-butanol

5. 15 15-5 © 2003 Thomson Learning, Inc. All rights reserved Enantiomers one way to see that the mirror image of 2-butanol is not superposable on the original is to rotate the mirror image

6. 15 15-6 © 2003 Thomson Learning, Inc. All rights reserved 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 enantiomersnonsuperposable mirror images are enantiomers

7. 15 15-7 © 2003 Thomson Learning, Inc. All rights reserved Enantiomers chiral 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 stereocentera carbon with four different groups bonded to it is called a stereocenter

8. 15 15-8 © 2003 Thomson Learning, Inc. All rights reserved Enantiomers If an object and its mirror image are superposable, they are identical and there is no possibility of enantiomerism achiralwe say that such an object is achiral (without chirality) As an example of an achiral molecule, consider 2- propanol notice that it has no stereocenter

9. 15 15-9 © 2003 Thomson Learning, Inc. All rights reserved Enantiomers to see the relationship between the original and its mirror image, rotate the mirror image by 120° when we do this rotation, we see that 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

10. 15 15-10 © 2003 Thomson Learning, Inc. All rights reserved Enantiomers To summarize chiralobjects that are nonsuperposable on their mirror images are chiral (they show handedness) the most common cause of chirality among organic molecules is the presence of a carbon with four different groups bonded to it stereocenterwe call a carbon with four different groups bonded to it a stereocenter achiralobjects that are superposable on their mirror images are achiral (without chirality) enantiomersnonsuperposable mirror images are called enantiomers enantiomers always come in pairs

11. 15 15-11 © 2003 Thomson Learning, Inc. All rights reserved The R,S System 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

12. 15 15-12 © 2003 Thomson Learning, Inc. All rights reserved The R,S System The first step in assigning an R or S configuration to a stereocenter is to arrange the groups on the stereocenter in order of priority priority is based on atomic number the higher the atomic number, the higher the priority

13. 15 15-13 © 2003 Thomson Learning, Inc. All rights reserved

14. 15 15-14 © 2003 Thomson Learning, Inc. All rights reserved The R,S System Example:Example: assign priorities to the groups in each set

15. 15 15-15 © 2003 Thomson Learning, Inc. All rights reserved The R,S System Example:Example: assign priorities to the groups in each set

16. 15 15-16 © 2003 Thomson Learning, Inc. All rights reserved The R,S System To assign an R or S configuration 1.assign a priority from 1 (highest) to 4 (lowest) to each group bonded to the stereocenter 2.orient the molecule in space so that the group of lowest priority (4) is directed away from you; the three groups of higher priority (1-3) then project toward you 3.read the three groups projecting toward you in order from highest (1) to lowest (3) priority R S 4. if reading the groups 1-2-3 is clockwise, the configuration is R; if reading them is counterclockwise, the configuration is S

17. 15 15-17 © 2003 Thomson Learning, Inc. All rights reserved The R,S System example:example: assign an R or S configuration to each stereocenter

18. 15 15-18 © 2003 Thomson Learning, Inc. All rights reserved The R,S System example:example: assign an R or S configuration to each stereocenter

19. 15 15-19 © 2003 Thomson Learning, Inc. All rights reserved The R,S System returning to our original three-dimensional drawings of the enantiomers of ibuprofen

20. 15 15-20 © 2003 Thomson Learning, Inc. All rights reserved Two Stereocenters n 2 n For a molecule with n stereocenters, the maximum number of stereoisomers possible is 2 n we have already verified that, for a molecule with one stereocenter, 2 1 = 2 stereoisomers (one pair of enantiomers) are possible for a molecule with two stereocenters, a maximum of 2 2 = 4 stereoisomers (two pair of enantiomers) is possible for a molecule with three stereocenters, a maximum of 2 3 = 8 stereoisomers (four pairs of enantiomers) is possible and so forth

21. 15 15-21 © 2003 Thomson Learning, Inc. All rights reserved Two Stereocenters 2,3,4-trihydroxybutanal two stereocenters; 2 2 = 4 stereoisomers exist diastereomers:diastereomers: stereoisomers that are not mirror images (a) and (c), for example, are diastereomers

22. 15 15-22 © 2003 Thomson Learning, Inc. All rights reserved Stereoisomers example:example: mark all stereocenters in each molecule and tell how many stereoisomers are possible for each

23. 15 15-23 © 2003 Thomson Learning, Inc. All rights reserved Stereoisomers example:example: mark all stereocenters in each molecule and tell how many stereoisomers are possible for each solution:solution:

24. 15 15-24 © 2003 Thomson Learning, Inc. All rights reserved Stereoisomers The 2 n rule applies equally well to molecules with three or more stereocenters

25. 15 15-25 © 2003 Thomson Learning, Inc. All rights reserved Optical Activity Ordinary light: 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: Polarimeter: an instrument for measuring the ability of a compound to rotate the plane of plane- polarized light Optically active: Optically active: showing that a compound rotates the plane of plane-polarized light

26. 15 15-26 © 2003 Thomson Learning, Inc. All rights reserved Polarimeter

27. 15 15-27 © 2003 Thomson Learning, Inc. All rights reserved Optical Activity Dextrorotatory:Dextrorotatory: clockwise rotation of the plane of plane-polarized light Levorotatory:Levorotatory: counterclockwise rotation of the plane of plane-polarized light Specific rotation:Specific rotation: the observed rotation of an optically active substance at a concentration of 1 g/mL in a sample tube 10 cm long

28. 15 15-28 © 2003 Thomson Learning, Inc. All rights reserved Chirality in Biomolecules 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

29. 15 15-29 © 2003 Thomson Learning, Inc. All rights reserved 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

30. 15 15-30 © 2003 Thomson Learning, Inc. All rights reserved Chirality in Biomolecules how an enzyme distinguishes between a molecule and its enantiomer

31. 15 15-31 © 2003 Thomson Learning, Inc. All rights reserved 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, while its R enantiomer is inactive the S enantiomer of naproxen is the active pain reliever, but its R enantiomer is a liver toxin!

32. 15 15-32 © 2003 Thomson Learning, Inc. All rights reserved End Chapter 15 Chirality