1. Chem 125 Lecture 32 11/21/08 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. Is the Minimum eclipsed or staggered? 0°120° 240° 360° Torsional Angle Energy 3 kcal/mol

3. Latest Word Experiment cm -1 x 2.86 = cal/mole Quantum Theory (various approximations) ~2.7 kcal/mole ~2.9 kcal/mole p. 11191

4. But there are also p-e attractions. What is the source of the ~3 kcal/mole barrier in Ethane? (a) Eclipsed form destabilized or (b) Staggered form stabilized? (Compared to what?) H-H repulsion e-e repulsion only 3.4 kcal/mole for propane (so "size" of H is not very important) C C H H C H H H

5. + + _ + + _ What is the source of the ~3 kcal/mole barrier in Ethane? (a) Eclipsed form destabilized or (b) Staggered form stabilized? C C H H   HOMO/LUMO mixing C=C H+H+ H _ "hyperconjugation"

6. A Digression on Topicity (Placeness) H H CC O H H H H pK a ~16 pK a ~50 Yes, but their environments are different. These protons are “heterotopic” (Greek:  ó , topos = place) H H H H Protons within the blue (or green) set are “homotopic” and their properties Here we are discussing constitution; the distinctions are less trivial and more useful when they are stereochemical. Exchanges readily with acidic water D + : + + Are these two protons equivalent? Doesn’t exchange

7. diastereotopic H H H H Stereotopic Relationships These distinctions are only conformational. They are erased by rotation within ~10 -12 sec. H H CC O among atoms (or groups) that are constitutionally homotopic enantiotopic This distinction is configurational and lasts as long as bonds endure.

8. 43 2 1 H H H H Toponymy H H CC O among atoms (or groups) that are constitutionally homotopic enantiotopic H H H OHOH H H 34 pro-S pro-R Give higher priority to enantiotopic H being named. “prochiral” C (i.e. would be chiral, if the enantiotopic atoms differed)

9. Reactivity Difference? among atoms (or groups) that are constitutionally homotopic H H H OHOH H H pro-Spro-R Attacks by a reagent like Cl are mirror images and thus identical in rate. Cl

10. Reactivity Difference? among atoms (or groups) that are constitutionally homotopic H H H OHOH H H pro-Spro-R Attacks by a resolved chiral reagent are diastereomeric and should have different rates. Right

11. Establishing Enzyme Specificity H H H O-H D H If horse liver alcohol dehydrogenase (LAD) removes only the pro-R H from ethanol, it should remove H (never D) from (S)-1-deuteroethanol. LAD H H H O D + NADH + NAD + Good test, but where to get the (S)-1-deuteroethanol? By starting with same catalyst, CH 3 CDO and excess NADH. A full cycle Actually LAD is a catalyst for oxidation by “NAD +”. H+H+ returns CH 3 CDO with all of its initial D intact! [This proves specificity. Whether pro-R or pro-S required more work.]

12. Baeyer Strain Theory (1885) See https://webspace.yale.edu/chem125/125/history99/6Stereochemistry/Baeyer/strain https://webspace.yale.edu/chem125/125/history99/6Stereochemistry/Baeyer/strain l Academy of Science, Munich, 1893 Adolf von Baeyer

13. On Polyacetylene Compounds (1885) 1. Theory of Ring Closure and the Double Bond Ring closure is apparently the only phenomenon that can supply information about the arrangement of atoms in space. Since a chain of 5 or 6 members can be closed easily, while with one of more or fewer members it is difficult or impossible, spatial factors are apparently involved. They explode! (Dr. Homolka?)

14. The previously proposed general rules on the nature of carbon atoms are the following: I. Carbon is as a rule tetravalent. II. The four valences are equivalent, as shown by the fact that there is only one monosubstitution product of methane. III. The four valences are equivalently arranged in space and corres- pond to the corners of a regular tetrahedron inscribed in a sphere. IV. The atoms or groups attached to the four valences cannot exchange places. Evidence: there are two tetrasubstitution products abcd of methane, LeBel-van't Hoff Rule. V. Carbon atoms can bind to one another with 1, 2, or 3 valences. VI. These compounds can form either open or closed-ring chains.

15. I should like to add the following to these generally accepted rules: VII. The four valences of the carbon atom point in the directions connecting the center of the sphere to the corners of the tetrahedron, forming an angle of 109°28' with one another. The direction of attachment can undergo alteration, but a strain is generated increasing with the size of the deflection

16. Dimethylene is indeed the weakest ring, which can be opened by hydrogen bromide, bromine and even iodine; trimethylene is broken only by hydrogen bromide but not by bromine; finally tetramethylene and hexamethylene are difficult or impossible to break.

17. Sachse (1890)

19. "It is not possible to write an abstract of this paper, especially since the author's explanations are hardly understandable without models." Julius Wagner (1890)

20. Baeyer (1890) A further proposal is that the atoms in hexamethylene are arranged as in Kekulé's model, that is that the arrangement of the atoms in space is the one with a minimum distortion of the valence directions. Thus the 6 carbon atoms must lie in one plane and 6 hydrogen atoms lie in each of two equidistant parallel planes. Further each of the 12 hydrogen atoms must have the same position relative to the other 17 atoms. The experimental test of the correctness of this assumption is relatively easy, for example sufficient evidence is that there is a single isomer of hexahydrobenzoic acid [i.e. only one cyclohexane carboxylic acid]. Meanwhile, as long as our knowledge in this field is so incomplete, we must be satisfied that the above assumption is the most likely, and no known fact contradicts it.

21. Sachse (1892) 41 pp. in Zeitschrift für Physikalische Chemie edited by Ostwald, who did not believe in atoms and wrote dispar- agingly of his successor in Riga, "Scientifically he had been brought up in the narrow circle of contemporary organic chemistry, and to him the arrangement in space of the atoms of organic compounds was the foremost of all conceivable problems."

22. Sachse (1893) 34 pp. in Zeitschrift für Physikalische Chemie died at age 31 in 1893 Baeyer (1905) "Sachse…disagreed with my opinion that larger rings are planar. He is certainly right from a mathematical point of view; yet in reality, strangely enough, my theory appears to be correct. The reason is not clear…"

23. What important lesson should we all take from the tale of poor Sachse?

24. Sachse (1890)

25. Bragg & Bragg (1913) Diamond Structure by X-ray Ernst Mohr (1918)

26. End of Lecture 32 Nov. 21, 2008