Year 2 undergraduate Organic Chemistry. Mechanism and Stereochemistry Lecture 3 - Conformational Analysis of Cyclohexane.

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CH264/3
Organic Chemistry II
Cyclohexane Rings
Dr Andrew Marsh C515
a.marsh@warwick.ac.uk
Dr David J Fox B510
d.j.fox@warwick.ac.uk

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Today’s Lecture
1. Cyclohexane conformation
2. Drawing cyclohexane chairs
3. Monosubstituted cyclohexanes
4. Disubstituted cyclohexanes, decalins and steroids

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Angle strain in rings
24.5° 9.5° 0.5° -5° "angle strain" (divided between two ring bonds)
9.17 6.58 1.24 0.02
38.4 27.5 5.19 0.09
strain per CH2 group (kcal mol-1)
strain per CH2 group (kJ mol-1)
"angle strain" is (109° - ring angle)/2

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Cyclohexane is ‘strain free’
A planar arrangement of the six methylene groups in cyclohexane does not
give a tetrahedral shape for every carbon atom - this is achieved by puckering
the ring. Cyclohexane does this by adopting mainly two conformations the
CHAIR and the BOAT.
chair boat chair
CGW p.371

5. Conformational analysis
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Nobel Prize 1969

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Cyclohexane is ‘strain free’
HeqHeq
Heq
Hax
Ha
He
Hax
Hering flip
Heq Heq
HaxHax
view as Newman
projection
1,3-diaxial interaction
HeqHeq
Heq
HaxHax
Heq
view as Newman
projection
gauche interaction
109° angle allows near strain free cyclic molecule

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Substituents on cyclohexane
a a
aa
a
e
ee
e
e
e
axial substituents
equatorial substituents
a
CGW p. 371

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Ring Flip
Ha
He
He
Ha
Ha
He
He
Ha
Ha
He
Ha
He
Ha
He
Ha
He
twist
boat
half chair
Ha
He
Ha
He
Ha
He
Ha
He
Ha
He
Ha
He
boat
4
kJ mol-1
43
25
21
0

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Chair Conformer
Ha
He
He
Ha
Ha
He
Ha
He
view Ha
He
He
Ha
staggered
Ha
He
He
Ha
Ha
He
Ha
He
view Ha
He
He
Ha

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Boat Conformer
Ha
He
Ha
He
1,4-transannular interaction
H
H
H
H
He
Ha Ha
He
• eclipsing C-C bonds & C-H
• no C-H HOMO C-C LUMO donation
view

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Substituted Cyclohexanes
HeqHeq
He
Ha
Ha
He
Ha
H3C CH3
CH3
CH3
CH3
CH3
Hering flip
favoured conformer
Heq Heq
Hax
H3C CH3
CH3
view as Newman projection
unfavourable
gauche interaction
1,3-diaxial interaction
HeqHeq
Heq
HaxHax
CH3
CH3
CH3
conc equatorial conformer
conc axial conformer
K = >3000, >99.9% equatorial, >20 kJ mol-1
difference

12. Substituted cyclohexanes:
energy difference
Substituent K Axial – equatorial
energy difference
kJ mol-1
% equatorial
H 1 0 50
OMe 2.7 2.5 73
Me 19 7.3 95
Et 20 7.5 95
iPr 42 9.3 98
tBu >3000 >20 >99.9
110 110 11.7 99
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CGW p. 375

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Disubstituted cyclohexanes
CH3
CH3
CH3
CH3
anti-1,3-dimethylcyclohexane
syn-1,3-dimethylcyclohexane
H3C
CH3
CH3
CH3
H3C CH3
CH3
CH3
favoured
cis-
trans-
H
H
H
H

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The tert-butyl group is a
conformational ‘lock’
OH
OH
OH
H
H
cis-4-t-butylcyclohexanol
trans-4-t-butylcyclohexanol
H
OH
H
OH
H
H
H
OH
H

15. Decalins
H
H
H
trans-decalin
conformationally locked
Ha
cis-decalin
H
H
H
He
CGW p. 378

16. Steroids: cholestanol
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Conformationally locked A–B–C–D rings
HHO
H
Me
Me
Me
HO
H
H
H
H
H
A B
C D
CGW p. 379

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You should be able to:
(i) Draw cyclohexane as chair conformers
(ii) Ring-flip monosubstituted cyclohexane
(iii) Show which conformer is favoured in mono- and di-
substituted cyclohexanes
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