1. Chem 125 Lecture 26 11/5/08 This material is for the exclusive use of Chem 125 students at Yale and may not be copied or distributed further. It is not readily understood without reference to notes or the wiki from the lecture.

2. van't Hoff’s Optically Active Compounds Malic Acid (CO 2 H)CH(OH).CH 2. (CO 2 H) Lactic Acid (CH 3 )CH(OH)(CO 2 H) Tartaric Acid (CO 2 H)CH(OH).CH(OH)(CO 2 H) Aspartic Acid (CO 2 H)CH(NH 2 ).CH 2. (CO 2 H) Amyl Alcohol (CH 3 )(C 2 H 5 )CH(CH 2 OH) Glucose COH(CHOH) 4 CH 2 (OH) (Levulose, Lactose) Maleic & Fumaric Acids (CO 2 H)HC=CH(CO 2 H)    (CO 2 H)CH 2 CH 2 (CO 2 H) Succinic Acid HI/P OH  H “reduction” (Bremer & van't Hoff) & Most of their Derivatives, but not inactive Scheele Liebig Wislicenus (Scheele, Berzelius, Pasteur, Wislicenus) right, left, and inactive Encyclopaedia Britannica, 1911: LACTIC ACID (hydroxypropionic acid), C 3 H 6 O 3. Two lactic acids are known, differing from each other in the position occupied by the hydroxyl group in the molecule; they are known respectively as  -hydroxypro- pionic acid (fermentation, or inactive lactic acid), CH 3 CH(OH). CO 2 H, and 3-hydroxypropionic acid (hydracrylic acid), CH 2 (OH)CH 2 CO 2 H. Although on structural grounds there should be only two hydroxypro- pionic acids, as a matter of fact four lactic acids are known. The third isomer (sarcolactic acid) is found in meat extract (J. v. Liebig), and may be prepared by the action of Penicillium glaucum on a solution of ordinary ammonium lactate. Constututional Isomers It is identical with  -hydroxypropionic acid in almost every respect, except with regard to its physical properties. The fourth isomer, formed by the action of Bacillus laevo-lacti on cane-sugar, resembles sarcolactic acid in every respect, except in its action on polarized light. “…the fancy trifles in it are totally devoid of any factual reality…” Kolbe on van’t Hoff (1877) !

3. van't Hoff Obituary (1911) In his whole life he never made what would be called a very accurate measurement, and he never cared to. I remember his saying to me eighteen years ago, “How fortunate it is that there are people who will do that sort of work for us!”

4. (CO 2 H)CH 2 CH 2 (CO 2 H) Succinic Acid “reduction” (Bremer & van't Hoff) & Most of their Derivatives, but inactive van't Hoff’s Optically Active Compounds Malic Acid (CO 2 H)CH(OH).CH 2. (CO 2 H) Lactic Acid (CH 3 )CH(OH)(CO 2 H) Tartaric Acid (CO 2 H)CH(OH).CH(OH)(CO 2 H) Aspartic Acid (CO 2 H)CH(NH 2 ).CH 2. (CO 2 H) Amyl Alcohol (CH 3 )(C 2 H 5 )CH(CH 2 OH) Glucose COH(CHOH) 4 CH 2 (OH) (Levulose, Lactose) Maleic & Fumaric Acids (CO 2 H)HC=CH(CO 2 H)  "Every carbon compound which in solution can rotate the plane of polarized light contains one or more asymmetric carbon atoms."

5. 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

6. Maleic and Fumaric Acids

7. 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.

8. van’t Hoff predicts handedness 1874

9. 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

10. 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 ?

11. 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

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

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

14. “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?)

15. “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 (1894) Chirality (Greek “  ” hand)

16. Change Sign of all X Coordinates?

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

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

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

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

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

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

23. Inversion through Center of Symmetry

24. 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.

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

26. 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.

27. 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

28. 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

29. 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.)

30. Beyond Constitutional Isomerism (Stereochemistry) Composition Constitution "Stereoisomers" distinction based on 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)

31. Stereochemical Relationships Two molecules with the same constitution can be: Identical Completely Different Mirror Images (Homomers) Diastereomers Enantiomers

32. Facts Ideas Words (pictures too)

33. 3D Clues in Model Pictures Stereo, Rotation, Size, Perspective, Shading, Obstruction, Highlight, Wedge-Dash, etc.

34. End of Lecture 26 Nov. 5, 2008