1. Chemistry 125: Lecture 26 November 4, 2009 van’t Hoff’s Carbon & Chirality; Communicating Configuration With his tetrahedral carbon models van’t Hoff explained the mysteries of known optical isomers possessing stereogenic centers and predicted the existence of chiral allenes, a class of molecules that that would not be observed for another 61 years. Symmetry operations that invert an odd number of coordinate axes interconvert mirror-images. Like printed words, only a small fraction of molecules are achiral. It is important for chemists to agree on notation and nomenclature in order to communicate molecular constitution and configuration. It is best when a diagram is as faithful as possible to the 3D shape of a molecule, but the conventional 1891 Fischer projection, which has been indispensable in understanding sugar configurations for over a century, involves highly distorted bonds. For copyright notice see final page of this file

2. van’t Hoff Cardboard Models ( Bremer’s set, in Museum Boerhaave, Leiden) (from T. M. van der Spek, Annals of Science, 2006) Colored Faces Colored Vertices Ladenburg Benzenes

3. Fumaric and Maleic Acids

4. Free Rotation : Tartaric / meso van’t Hoff made this diagram to show that free rotation about the central bond results in rapid interconversion (and thus inseparability and irrelevance) of “Patern ó isomers.” Note that R 1,R 2,R 3 (and R 4,R 5,R 6 ) can be arranged clockwise or counterclockwise about the C-C axis. This sequence is permanent and unaffected by C-C rotation. If R 1 =R 4, R 2 =R 5, R 3 =R 6, as in tartaric acid, there are three possible isomers: cw-cw, ccw-ccw, and cw-ccw. If 123≠456, there is a fourth isomer ccw-cw. For mesotartaric acid, there is no net effect on polarized light, because the ccw half cancels the cw half.

5. van’t Hoff predicts handedness of allenes 1874 C C C R RH H

6. C 10 H 7 C6H5C6H5 C6H5C6H5 61 years after van’t Hoff prediction of 1874 C6H5C6H5 OCOCH 2 COOH C C CC6H5C6H5 C 10 H 7 C6H5C6H5 tetrahedral bonds coplanar bonds? must break  bond to isomerize to mirror image C6H5C6H5 OCOCH 2 COOH C C C C6H5C6H5 C 10 H 7

7. Isomer Numbers for “Dewar's” 3D Benzene Structures "Prismane" or "Ladenburg Benzene" "Dewar Benzene" 2(1) 3(2) 3(1) 6(3) 3(3) 5(4) 3(2) 1 9(6) 2(1) 3(2) 3(1) 6(3) 2(1) 5(3) 1 6(3) 2(1) 3(2) 3(1) 6(3) 3(2) 2 5(2) 1 3(1) MONO DI (additional number if mirror-images count for these nonplanar structures) (subtotals with total in Red) 3(1) assuming free rotation of CH 3 0 top 0 mid 0 bottom 0 total ?

8. which our intuition interprets as rotation about the vertical axis (exchanging right and left), because people pivot, but don’t "invert". It exchanges front and back, Mirror Images Q. Why does a mirror exchange right. and left, but not top and bottom? A. Actually it changes neither. Right is Top on top is on right

9. special.lib.gla.ac.uk/ exhibns/month/mar2000.html Right Arm Oxford Mathematician blind in one eye

10. special.lib.gla.ac.uk/ exhibns/month/mar2000.html Right ArmLeft Arm

11. “Well then, the books are something like our books, only the words go the wrong way; I know that, because I've held up one of our books to the glass, and then they hold up one in the other room… "Now, if you'll only attend, Kitty, and not talk so much, I'll tell you all my ideas about Looking-glass House… "How would you like to live in Looking-glass House, Kitty? I wonder if they'd give you milk, there? “Perhaps Looking-glass milk isn't good to drink. E. Heilbronner, J.D. Dunitz, Reflections on Symmetry, 1993, p. 86 (sarcolactic?)

12. “I call any geometrical figure, or group of points, chiral, and say that it has chirality, if its image in a plane mirror, ideally realized, cannot be brought to coincide with itself.” Lord Kelvin (1893) Chirality (Greek “  ” hand)

13. Change Sign of all X Coordinates?

14. Reflection in yz Mirror Change Sign of all Y Coordinates?

15. Reflection in xz Mirror Change Sign of all Z Coordinates?

16. Reflection in xy Mirror Change Sign of all X & Y Coordinates?

17. Rotation about z Axis Change Sign of all X & Z Coordinates?

18. Rotation about y Axis Change Sign of all Y & Z Coordinates?

19. Rotation about x Axis Change Sign of all X & Y & Z Coordinates?

20. Inversion through Center of Symmetry

21. Chirality - Non-superimposable Mirror Images The right hand has only one mirror image, but different mirrors (or the inversion center) generate it in different orientations.

22. How Special is Chirality? Democratic Answer: Class voted overwhelmingly that there should be more achiral than chiral molecules (Vox Populi, Vox Dei) Pretty special

23. 2-D Chirality of Words MUM is its own mirror image. Thus it is “achiral” or “meso” Mirror by changing sign of X NOON is not its own mirror image. Thus it is “chiral” like most of the words.

24. 2-D Chirality of Words Rotate by changing signs of X and Y NOON does have rotational symmetry, but still it is chiral, like a propeller

25. 2-D Chirality of Words DECODE is also an “achiral” “meso” word, but it is harder to recognize, because horizontal mirrors are unfamiliar. Mirror by changing sign of Y

26. How Special is Chirality? Almost all words are chiral. Achiral or meso words, such as MUM and DECODE are very rare. It is the same with molecules. Almost all molecules are chiral. Not at all. (But when we deal with very simple molecules, we often encounter achiral or meso ones.)

27. Beyond Constitutional Isomerism (Stereochemistry) Composition Constitution "Stereoisomers" The distinction between configuration & conformation is based on our bonding model. Change requires breaking bonds (van't Hoff) Change by rotating about single bonds (Paternó) Isomers Configuration Conformation HARD EASY All "isomers" represent local energy minima (not just different phases of vibration)

28. Stereochemical Relationships Two molecules with the same constitution can be: Identical Completely Different Mirror Images (Homomers) Diastereomers Enantiomers (enantios - opposite) (dia - across)

29. Facts Ideas Words (pictures too) Stereochemical

30. 3D Clues in Model Pictures Size, Perspective, Obstruction Rotation, Highlight, Shading, etc., Stereo-Pair

31. Notation: Using Dashes and Wedges to Show Tetrahedral Carbons Planar <90° Angle 90° & 180° Angles OK (Conventional) OK 109° angles

32. "Fischer Projection" (1891) With the help of Friedländer's convenient rubber models, one can construct molecules of right-handed tartaric acid, left-handed tartaric acid, and inactive tartaric acid and lay them in the plane of the paper so that the four carbon atoms are in a straight line and the attached hydrogens and hydroxyls lie above the plane of the paper: Bent to go back from BOTH atoms Rotate 90°

33. "Fischer Projection" (1891) May rotate in-plane by 180° but NOT by 90° because horizontal bonds are taken as wedges enantiomersdiastereomers  “meso” names of relationships Its own mirror image name was generalized “inactive” (between + & - ?)

34. Configurational Isomer Counting n "Stereogenic Centers"  2 n isomers ? No, because of meso compounds "Next we consider a symmetrical formula: C(R 1 R 2 R 3 )C(R 4 R 4 )C(R 1 R 2 R 3 ), and C(R 1 R 2 R 3 )C(R 4 R 5 )C(R 1 R 2 R 3 ) as well. As is easily conceived from the forgoing discussion, they lead to only three isomers." van't Hoff (1877) (Baeyer & Fischer gave up on using bread rolls.)

35. End of Lecture 26 Nov. 4, 2009 Copyright © J. M. McBride 2009. Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0) Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol. Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0