1. 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.
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2. Sachse (1890)

3. 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.

4. 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."

5. 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…"

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

7. Sachse (1890)

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

9. Ernst Mohr Illustrations (1918)
flagpole
bowsprit
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:
inverted
chair
“ring flip” by 60° counter-rotation
of two parallel bonds

10. 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

11. Cholic Acid
(a Steroid)
Glucose
(a Carbohydrate)

12. 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)

13. 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”)

14. 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!

15. Mol4D (CMBI Radboud University, Nijmegen, NL)
Conformational Jmol Animations
Click for INDEX or go to
(see Wiki to install Jmol)

16. Mol4D (CMBI Radboud University, Nijmegen, NL)
Ethane Click to Animate or go to
Click Points
Staggered
Step Keys
Eclipsed barrier ~5.2 kJ/mol  = 1.24 kcal/mol
Should be ~2.9 kcal/mol. Caveat emptor!

17. Mol4D (CMBI Radboud University, Nijmegen, NL)
Propane Click to Animate or go to
Eclipsed
3.3 kcal/mol
Staggered

18. Mol4D (CMBI Radboud University, Nijmegen, NL)
Butane (central bond) Click to Animate or go to
Anti Gauche+
1013 10 -3/4  3.4 = /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 = = 1 / 4.7
Gauche / Anti = 2  10 -3/4  0.9 = 2  = 1 / 2.4

19. 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

20. Mol4D (CMBI Radboud University, Nijmegen, NL)
Ring Flip of c-Hexane Click to Animate or go to
Barrier (Half-Chair)
~ 11 kcal/mol
Flexible or
Twist-Boat conformer
~5.5 kcal/mol
Chair conformer

21. Mol4D (CMBI Radboud University, Nijmegen, NL)
Flexible c-Hexane Click to Animate or go to
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.

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

23. 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 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 kcal/mol

24. End of Lecture 34 Dec. 1, 2010
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