1. Chemistry 125: Lecture 25 November 1, 2010 Arrangement in Space; “Optical” Isomers & Chirality (1848,1874-1877) Despite cautions from their conservative elders, young chemists like Paternó and van’t Hoff began interpreting molecular graphs in terms of the arrangement of a molecule’s atoms in 3-dimensional space. Benzene was one such case, but still more significant was the prediction, based on puzzling isomerism involving “optical activity”, that molecules could be “chiral”, that is, right- or left-handed. Louis Pasteur effected the first artificial separation of racemic acid into tartaric acid and its mirror-image. 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. For copyright notice see final page of this file

2. Kekulé Ghent (1865) Koerner age 26 Proving Structure Albert Ladenburg age 23

3. Remarks on the Theory of Aromaticity Albert Ladenburg (1869, age 27) Already several years ago I had the occasion to make Kekulé aware that his graphical formula for benzene is not adequate, since here 1.2 and 1.6 must be inequivalent, while one could have various views on the identity of positions 3 and 5. Both conditions could however be fulfilled through alternative formulas which, so far as I know, have not been proposed before Kekulé adopts two hypotheses… 1.The 6 hydrogen atoms of benzene are equivalent 2.Each hydrogen atom of benzene has two sets of two others which are symmetrically arranged with respect to it… 1.2 = 1.6 1.3 = 1.5

4. Bonn (1872) Kekulé van't Hoff (age 20)

5. Proof that the prism formula suffers from the same problem as the hexagon with fixed double bonds removes the previously asserted superiority from the former and makes the original Kekulé notation not only simpler, but also the presentation with which the facts conform best. Ladenburg's Benzene Formula J. H. van't Hoff (1876, age 24) although differing from 4,5; 2,3; and 6,1. Exactly the same thing happens in Ladenburg's formula. An adequate consideration shows that I and II are absolutely different. A 1,3 product is different according to whether A or B occupies position 1. Dashed lines to show 3D The 1,2; 5,6; and 3,4 deriva- tives are completely similar,

6. On Benzene Formulas A. Ladenburg (1877) I cannot agree with him in this. Van't Hoff is dragging some- thing into the formulas which I together with most chemists expressly exclude. van't Hoff finds the two formulas below "absolutely" different. The formula takes account of the composition, molecular weight, and mode of union of the atoms. CONSTITUTION No BrokenLines Not 3D, just a Constitutional graph I refer to arrangement in space…

7. On Benzene Formulas A. Ladenburg (1877) Even van't Hoff will have to find that these two formulas are "absolutely" identical. If van't Hoff's view of space really will not tolerate the two formulas above to be identical, then I invite him, for his own special purposes, to use a different benzene formula, which was proposed by me in the year 1869 (when I compared the hexagon and the prism for the first time) together with the prism, to which it is for me certainly identical. It is the so-called Cross of David. Identical: as abstract 2D graph

8. Kohler 1920s/1 Harvard Organic Notes (1920s) Prof. E. P. Kohler (from R. M. Fuoss) Greek alpha, , means on carbon next to C=O Typically easy to substitute

9. Kohler 1920s/2 Harvard Organic Notes (1920s) Prof. E. P. Kohler (from R. M. Fuoss)

10. "1276" cm -1 Vibration Calculated by MO Theory (Spartan) Structure of mimimum potential energy + “Breathing”“Kekulé Distortion” of single minimum! "1367" cm -1

11. Might “stressful” substitution favor "Kekulé Distortion"? (forcing alternating bond lengths at energy minimum) Energy If We Force One Bond to Stretch ?

12. Might “stressful” substitution favor "Kekulé Distortion"? (alternating bond lengths at energy minimum) Careful X-Ray at -170°C (R. Boese, J. S. Siegel, 1988) 1.402 1.391 1.387 (±0.001Å) Not Here! long short long short ?

13. Genealogy Top L. PASTEUR-F resolution

14. It is hard to PROVE two samples identical (There could always be another test) Carvone Samples Boiling Points b.p. 230-231°C Infrared Spectra "identical" NMR Spectra "identical" Odor rye bread (carraway) spearmint ? Densities d 20 0.9652 g/mL Refractive Indices n 20 1.4988 D

15. 90°135° Suppose Blue Light is rotated more than Red Light. Suppose the sample between the filters “rotates” or “twists” the polarization. Some Materials (like Karo Syrup) Have the Ability to “Rotate” Polarized Light Polarizer 0° Analyzer 0°45° D [  ] 20 Specific Rotation ° / g/mL / dm temp (solvent should be specified) color Note: the arrow in this animation denotes the direction of the light’s electric field, NOT the image seen.

16. It is hard to PROVE two samples identical (There could always be another test) Carvone Samples Boiling Points b.p. 230-231°C Infrared Spectra "identical" NMR Spectra "identical" Odor rye bread (carraway) spearmint ? Densities d 20 0.9652 g/mL Refractive Indices n 20 1.4988 D Specific Rotation +62 -62 [  ] 20 D

17. Constitutional Formulae of Carvone Models with Tetrahedral Carbon longhand shorthand s?s? unlike vs. back forward H orientation Is this difference real?

18. Isomers of Tartaric Acid (CO 2 H)CH(OH).CH(OH)(CO 2 H) 0 [  ] 20 13 D meso-Tartaric Acid "Pyrotartaric" 140°  0 Racemic Acid 206° Tartaric Acid 170°d-(+)- mp(°C) Berzelius (1830)

19. Problems with the Model ISOMER NUMBERS Maleic & Fumaric Acids HOOCCH=CHCOOH dextro & levo Lactic Acids (CH 3 )CH(OH)COOH Tartaric & Racemic Acids HOOCCH(OH)CH(OH)COOH & meso-Tartaric Too Few Predicted: & l-Tartaric ! Paternó’s Dibromoethanes Too Many Predicted: Kekulé’s 2-Propanols

20. Louis Pasteur (1822-1895) budding chemistry-physics- crystallography interdisciplinarian "On the relations that can exist among crystalline form, chemical composition and the direction of rotatory polarization" 1848 http://www.lmcp.jussieu.fr/~soyer/cristallo/pasteur_l.html

21. Eilhard Mitscherlich (1794-1863) Goniometer to Measure Crystal Angles

22. Figure 9 (CO 2 Na)CH(OH).CH(OH)(CO 2 NH 4 ) Tartrate: "The eight f edges should be modified in the same way, Racemate: I carefully separated the right from the left crystals, and observing their dissolution separately with M. Biot's polarization apparatus, I saw with surprise and delight that the [right] crystals deviated the plane of polarization to the right, and the [left] to the left." but always only [the same] four of them are facetted." "…as often to the right as to the left on different crystals… Mitscherlich had reported that this optically inactive salt was isomorphous with the tartrate. Shouldn’t crystals from ‘untwisted’ molecules be “holohedral” and show all eight f-facets?

23. Isomers of Tartaric Acid (CO 2 H)CH(OH).CH(OH)(CO 2 H) meso-Tartaric Acid "Pyrotartaric" 140°  0 Racemic Acid 206° Tartaric Acid 170°d-(+)- mp(°C) 0 [  ] 20 +13 l-(-)-Tartaric Acid 170°-13 d and l are mirror images (50:50) ? Resolution (by Pasteur - 1848)

24. Kekulé van't Hoff age 20 Bonn (1872) Fast Forward 24 Years !

25. J. H. van't Hoff (1852-1911) First Nobel Prize (1901) Hero: Lord Byron Most Admired Trait: Imagination (poets/artists) 1874 - Student

26. (12 pp.) 1874 6 days after van’t Hoff’s 22 nd birthday Proposal for the Extension of Current Chemical Structural Formulas into Space, together with Related Observation on the Connection between Optically Active Power and the Chemical Constitution of Organic Compounds Voorstel tot Uitbreiding der Tegenwoordige in de Scheikunde gebruikte Structuurformules in de Ruimte, benevens een daarmee samenhangende Opmerking omtrent het Verband tusschen Optisch Actief Vermogen en chemische Constitutie van Organische Verbindingen from the collection of G. S. Girolami & V. V. Mainz, by permission

27. (43 pp.) 1875 CHEMISTRY IN SPACE The facts require that the difference between isomeric molecules with the same structural formula be explained by different arrangements of the atoms in space. Wislicenus from the collection of G. S. Girolami & V. V. Mainz, by permission

28. THE ARRANGEMENT OF ATOMS IN SPACE 1877 53 pp. See website for: (1) van't Hoff's Tetrahedral Carbon (2) Kolbe's Criticism of van't Hoff (3) Your Teacher, a later-day Kolbe? “It is completely impossible to criticize this booklet in any detail because the fancy trifles in it are totally devoid of any factual reality and are completely incomprehensible to any clear- minded researcher… The brochure begins with the words: "The modern chemical theory has two weak points. It says nothing either about the relative position or the motion of the atoms within the molecule.” Hermann Kolbe (age 56)

29. van't Hoff’s Optically Active Compounds Scheele Liebig Wislicenus Constututional Isomers “…the fancy trifles in it are totally devoid of any factual reality…” Kolbe on van’t Hoff (1877) ! Inactive Hydracrylic Encyclopaedia Britannica (1911) - authoritative article by van’t Hoff ) Right Left Lactic Acid (CH 3 )CH(OH)(CO 2 H)

30. van't Hoff’s Optically Active Compounds Malic Acid (CO 2 H)CH(OH).CH 2. (CO 2 H) 2 Tartaric Acids (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) (also Levulose, Lactose) (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 2 Lactic Acids (CH 3 )CH(OH)(CO 2 H) Scheele Liebig Wislicenus Maleic & Fumaric Acids (CO 2 H)HC=CH(CO 2 H)     (Scheele, Berzelius, Pasteur, Wislicenus), but not

31. 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!”

32. Malic Acid (CO 2 H)CH(OH).CH 2. (CO 2 H) 2 Lactic Acids (CH 3 )CH(OH)(CO 2 H) 2 Tartaric Acids (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) (CO 2 H)CH 2 CH 2 (CO 2 H) Succinic Acid “reduction” (Bremer & van't Hoff) & Most of their Derivatives, but not inactive van't Hoff’s Optically Active Compounds (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." C C C C C C C

33. 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

34. End of Lecture 25 Nov. 1, 2010 Copyright © J. M. McBride 2009,2010. 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