Chemistry 125: Lecture 34December 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)

relatively easy, for example sufficient evidence is that there is a single isomer of hexahydrobenzoic acid [i.e. only one cyclohexane carboxylic

acid].

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 isrelatively easy,

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 fürPhysikalische 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 fürPhysikalische 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)

“chair” “boat”

bowsprit

flagpole

“ring flip” by 60° counter-rotation

of two parallel bonds

Red bonds rotate in & up. Blue bonds rotate in & down.

invertedchair

ww

w. d

ownu

nder

chic

ago.

com

/pic

s/ol

-la-

lafu

ma-

recl

iner

--pa

dded

--la

.jpg

http://beothic.blogspot.com/2007/01/dory_13.htm

l

Ernst Mohr Illustrations (1918)

Drawing “Ideal” Chair Cyclohexane:

opposite C-C bonds are parallel

axial bonds are parallel to 3-fold axis

equatorial bonds are (anti)parallelto next-adjacent C-C bonds

Whato’clock?

??

??Z

Cholic Acid(a Steroid)

Glucose(a Carbohydrate)

For such problems D.H.R. Barton Invents Conformational Analysis (1950)

Baeyer observed only one c-Hexyl-COOH, but in theseepimers, and OH groups have different reactivity!

“up” ; “down” (for molecule in conventional orientation,

old-fashioned configuration notation, like cis / trans)

Barton redraws Ring A

Intermediates in steroid hormone synthesis

A B

C D

(configurationally diastereotopic)

(e) “equatorial”

(p) “polar” (now axial)

Cf. ~1950 Stereochemistry:Bijvoet, Newman, CIP,(Molecular Mechanics)

(Nobel Prize 1969 for “development of the concept of conformation and its application in chemistry”)

ERRORS? “up” ; “down”

(for molecule in conventional orientation, old-fashioned configuration notation, like cis / trans)

3-fold axis

For such problems D.H.R. Barton Invents Conformational Analysis (1950)

)

Ring Flip?

Ernst Mohr Illustrations (1918)

Ring flip impossible for trans decalin!

N.B. During ring flip equatorials become axials

and vice versa.

anti

gauche

gauche, but not anti, is OK for the second ring of decalin.

fused chairs in "decalin"(decahydronaphthalene)

Try with modelsif you’re skeptical.

Mol4D(CMBI Radboud University, Nijmegen, NL)

Click for INDEX or go to http://cheminf.cmbi.ru.nl/wetche/organic/index.html

Conformational Jmol Animations

(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

Eclipsed barrier ~5.2 kJ/mol 0.239 = 1.24 kcal/molShould be ~2.9 kcal/mol. Caveat emptor!

Step Keys

Click Points

Staggered

Mol4D(CMBI Radboud University, Nijmegen, NL)

Propane Click to Animate or go to http://cheminf.cmbi.ru.nl/wetche/organic/nalkanesconf/propane/jmproprot.html

Staggered

Eclipsed3.3 kcal/mol

Anti Gauche+

1013 10 -3/4 3.4 = 10 10.5 /sec

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

Gauche0.9 kcal/mol(tells how much)

eclipsed3.5 kcal/mol(tells how fast)

fully eclipsed~ 5.5 kcal/mol?

(experimentally irrelevant)

Anti

Gauche / Anti = 10 -3/4 0.9 = 10-0.68 = 1 / 4.7Gauche / Anti = 2 10 -3/4 0.9 = 2 10-0.68 = 1 / 2.4

+

+

Gauche-

H

H HH

H HH

H HH

H H

H

HH

H

H H

H

HH

H

H H

H

HH

H

H HH

H HH

H H

H

HH

H

H H

3 3 3

Conformational Energy of EthaneButane5.5

0.9(0.6?)

5.5

0.9(0.6?)

3.5

H

H HH

H HH

H HH

H H

H

HH

H

H H

H

HH

H

H H

H

HH

H

H HH

H HH

H H

H

HH

H

H H

CH3CH3 CH3

CH3

CH3 CH3

CH3

CH3 CH3 CH3CH3

CH3CH3

CH3

H H

3.5

0° 120° 240° 360°Torsional Angle

Ene

rgy

(kca

l/m

ole)

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

Flexible or Twist-Boat conformer

~5.5 kcal/mol

Barrier (Half-Chair)~ 11 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

Flexible or Twist-Boat Form

Barrier (Boat)~ 1 kcal/mol

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)

Activation Energy for Racemizationobs. 19.5 kcal/mol

calc. 17.3 kcal/mol

At the barrier the C-C-Br angles

open by 12°.

t1/2 = 9 min at 0°C(1013 10-(3/4)*20 ~ 10-2/sec)

Question:How did having

COOH groups on the benzene rings

facilitate the experiment?

End of Lecture 34Dec. 1, 2010

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