Chemistry 125: Lecture 34 December 1, 2010 Cyclohexane & the Conformation of Cycloalkanes When Baeyer suggested strain-induced reactivity due to distorting bond angles away from those in an ideal tetrahedron, he assumed that the cyclohexane ring is flat. He was soon corrected by clever young Hermann Sachse, but Sachse’s weakness in rhetoric led to a quarter-century of confusion. Understanding conformational relationships makes it easy to draw idealized chair structures for cyclohexane and to visualize axial-equatorial interconversion. The conformational energy of cyclic alkanes illustrates the use of molecular mechanics, a useful, but highly empirical scheme for reckoning conformational energy. For copyright notice see final page of this file

Sachse (1890)

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, 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.

Sachse (1892) 41 pp. in Zeitschrift für Physikalische Chemie edited by Ostwald, who did not believe in atoms and wrote disparagingly 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."

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…"

What important lesson should we all take from the tale of poor Sachse? Write for your readership!

Sachse (1890)

Bragg & Bragg (1913) Diamond Structure by X-ray Ernst Mohr Illustrations (1918) confirm Sachse’s 1890 insight.

Ernst Mohr Illustrations (1918) flagpole bowsprit http://beothic.blogspot.com/2007/01/dory_13.html www. downunderchicago.com/pics/ol-la-lafuma-recliner--padded--la.jpg “chair” “boat” Red bonds rotate in & up. Blue bonds rotate in & down. Recliner: www. downunderchicago.com/pics/ol-la-lafuma-recliner--padded--la.jpg Newfoundland Dory: http://beothic.blogspot.com/2007/01/dory_13.html inverted chair “ring flip” by 60° counter-rotation of two parallel bonds

Ernst Mohr Illustrations (1918) What o’clock? ? Z ? ? ? Drawing “Ideal” Chair Cyclohexane: opposite C-C bonds are parallel axial bonds are parallel to 3-fold axis equatorial bonds are (anti)parallel to next-adjacent C-C bonds

Cholic Acid (a Steroid) Glucose (a Carbohydrate)

For such problems D.H.R. Barton Invents Conformational Analysis (1950)  “up” ;   “down” (for molecule in conventional orientation, old-fashioned configuration notation, like cis / trans) Intermediates in steroid hormone synthesis Barton redraws Ring A A B C D   Baeyer observed only one c-Hexyl-COOH, but in these epimers,  and  OH groups have different reactivity! (configurationally diastereotopic)

For such problems D.H.R. Barton Invents Conformational Analysis (1950)  “up” ;   “down” (for molecule in conventional orientation, old-fashioned configuration notation, like cis / trans) ERRORS? ) (e) “equatorial” (p) “polar” (now axial) Ring Flip? Cf. ~1950 Stereochemistry: Bijvoet, Newman, CIP, (Molecular Mechanics) 3-fold axis (Nobel Prize 1969 for “development of the concept of conformation and its application in chemistry”)

Ernst Mohr Illustrations (1918) gauche, but not anti, is OK for the second ring of decalin. anti N.B. During ring flip equatorials become axials and vice versa. gauche fused chairs in "decalin" (decahydronaphthalene) Try with models if you’re skeptical. Ring flip impossible for trans decalin!

Mol4D (CMBI Radboud University, Nijmegen, NL) Conformational Jmol Animations Click for INDEX or go to http://cheminf.cmbi.ru.nl/wetche/organic/index.html (see Wiki to install Jmol)

Mol4D (CMBI Radboud University, Nijmegen, NL) Ethane Click to Animate or go to http://cheminf.cmbi.ru.nl/wetche/organic/nalkanesconf/ethane/jmindex.html Click Points Staggered Step Keys Eclipsed barrier ~5.2 kJ/mol  0.239 = 1.24 kcal/mol Should be ~2.9 kcal/mol. Caveat emptor!

Mol4D (CMBI Radboud University, Nijmegen, NL) Propane Click to Animate or go to http://cheminf.cmbi.ru.nl/wetche/organic/nalkanesconf/propane/jmproprot.html Eclipsed 3.3 kcal/mol Staggered

Mol4D (CMBI Radboud University, Nijmegen, NL) Butane (central bond) Click to Animate or go to http://cheminf.cmbi.ru.nl/wetche/organic/nalkanesconf/butane/jmindex.html Anti Gauche+ 1013 10 -3/4  3.4 = 10 10.5 /sec fully eclipsed ~ 5.5 kcal/mol? (experimentally irrelevant) eclipsed 3.5 kcal/mol (tells how fast) + Anti Gauche 0.9 kcal/mol (tells how much) Gauche- Gauche / Anti = 10 -3/4  0.9 = 10-0.68 = 1 / 4.7 Gauche / Anti = 2  10 -3/4  0.9 = 2  10-0.68 = 1 / 2.4

Conformational Energy of Ethane Butane 5.5 0.9 (0.6?) 3.5 CH3 H 0° 120° 240° 360° Torsional Angle Energy (kcal/mole) 3 e.g. Journal of Molecular Structure: THEOCHEMVolume 814, Issues 1-3, 15 July 2007, Pages 43-49

Mol4D (CMBI Radboud University, Nijmegen, NL) Ring Flip of c-Hexane Click to Animate or go to http://cheminf.cmbi.ru.nl/wetche/organic/cyclohexane/jm/chxjmol.html Barrier (Half-Chair) ~ 11 kcal/mol Flexible or Twist-Boat conformer ~5.5 kcal/mol Chair conformer

Mol4D (CMBI Radboud University, Nijmegen, NL) Flexible c-Hexane Click to Animate or go to http://cheminf.cmbi.ru.nl/wetche/organic/cyclohexane/jm/twist_boat.html Barrier (Boat) ~ 1 kcal/mol Flexible or Twist-Boat Form The boat is not an isomer (an energy minimum), it is a barrier on the pleasantly smooth path between twist-boat isomers.

Shape, “Strain Energy” & Molecular Mechanics “Hooke’s Law” for Strain Energy

Molecular Mechanics (1946) N. E. Searle and Roger Adams, JACS, 56, 2112 (1935) At the barrier the C-C-Br angles  open by 12°. Activation Energy for Racemization obs. 19.5 kcal/mol Question: How did having COOH groups on the benzene rings facilitate the experiment? t1/2 = 9 min at 0°C (1013  10-(3/4)*20 ~ 10-2/sec) calc. 17.3 kcal/mol

End of Lecture 34 Dec. 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). 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