CH221 CLASS 8
CHAPTER 4: STEREOCHEMISTRY OF ALKANES AND CYCLOALKANES,
CONTINUED
Synopsis. Some of the more important aspects of the conformational isomerism
and cis-trans isomerism of cyclohexane and its mono- and disubstituted
derivatives are discussed in this class. Fused ring systems like decalin and the
steroids are considered at the end.
Probably the most important non-aromatic ring systems are those based upon
cyclohexane, which includes many natural products, like steroids and
carbohydrates. The three conformers of cyclohexane that are free of angle strain
are shown below.
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
TWIST (SKEW) BOAT
CONFORMER
moderate torsional
and steric strain
front view
(Newman
formulas)
H
H
H
H
H
CHAIR CONFORMER
minimum torsional and
steric strain (all C-H
bonds are staggered)
H
H H
H
H H
H
H
"flagpole bonds"
H
H
H
H
H
H
H
H
H
BOAT CONFORMER
significant torsional strain
(C-H bonds eclipsed)
and steric strain
H
H
H
H
H
H
H
H
H
It can be seen that the order of stability is:
CHAIR > TWIST BOAT > BOAT
Indeed, the huge majority of cyclohexane derivatives have the chair conformer as
the most stable one. The conformational isomerism of cyclohexane can be
represented by an energy diagram:
It can be seen from this diagram that the energy barriers are sufficiently high to
allow separate existence for each conformer, but are not high enough to prevent
rapid interconversion at normal temperatures.
How to Draw the Chair Conformer of Cyclohexane Ring Systems
1.
DRAW THE SKELETON
head of
chair
foot of
chair
2.
DRAW THE AXIAL BONDS: these are drawn alternately UP and DOWN,
as shown
axial bonds point directly
up and down
3.
DRAW THE EQUATORIAL BONDS: There are drawn parallel to the C-C
bond, ONE CARBON ATOM REMOVED (either way round the ring), as below.
5
3
2
equatorial bonds point
slightly up and down
6
1
this equatorial bond is drawn
parallel to the C(2)-C(3) or
C(5)-C(6) bond
The completed drawing, showing all bonds to carbon, is shown below.
axial
equatorial
The Chair Conformers of Cyclohexane: Equatorial and Axial Bonds
There are TWO kinds of C-H bonds in the chair conformer of cyclohexane:
1. Equatorial bonds. These are arranged around the “equator” of
the ring. They point alternately slightly up and slightly down.
H
H
H
H
H
H
2. Axial bonds. These point directly along the axis that is
perpendicular to the “equator”. They point alternately directly up
and directly down.
H
H
H
H
H
H
We have seen earlier that the conformers of cyclohexane are in rapid equilibrium
at normal temperatures. This means that the chair conformers will be rapidly
inter-converting via the boat conformers:
H(ax)
via boat
conformers
H(eq)
H(eq)
H(ax)
The process is known as a RING FLIP and results in the interconversion of equatorial and axial bonds.
Interatomic Distances and Steric Strain in Equatorial and Axial Positions
Although equatorial hydrogen atoms on adjacent carbon atoms are about the
same distance apart (2.5 Å) as axial hydrogens on alternate carbon atoms (2.7
Å), the former point away from each other (they are staggered), whereas the
latter point in the same direction (they are eclipsed):
2.7 A
H
H
H
H
H
2.5 A
H
2.5 A
This means that the axial positions are more prone to overcrowding, with
resultant steric strain.
The Chair Conformer of Monosubstituted Cyclohexanes: Equatorial versus
Axial Substitution
The conformational isomerism of methylcyclohexane is shown below.
H
H
()
H
C
()
H
(ax)
H
= steric strain
H
ring flip
C
axial conformer
-minor (5%)
(eq)
H
H
equatorial conformer
-major (95%)
Significant steric cowding occurs in the axial conformer, involving the hydrogen
atoms of the axial methyl group and the ring axial hydrogen atoms at positions 3
and 5. No such interaction occurs in the equatorial conformer. Physical
measurements indicate that the position of equilibrium lies well over to the
equatorial conformer, as shown above. With larger substituents, the position of
equilibrium lies even further over to the equatorial conformer, so that the dynamic
interconversion of chair conformers (via ring flip) can be considered to be
effectively “frozen” or “locked”. See, for example, tert-butylcyclohexane, below
and see also the table following this.
CH3
H
C
CH3
CH3
H
CH3
C
axial conformer
<<1%
CH3
CH
equatorial conformer 3
>>99%

Table showing differences in energy (G for equatorially and axially substituted
cyclohexanes)
Substituent
G /kJmol-1
Me
Et
iPr
tBu
Ph
6.7-7.5
6.7-9.2
7.5-10
24
11
Br
Cl
OH
NH2
2.9
2.1
1.7-3.8
5.0-6.7
greater in polar
and protic solvents
COO-
9.7
(eg H2O, MeOH, etc)
CO2Et
5-5.8
OCOMe
1.5
Comments
Summary: 1. The chair conformers of cyclohexane are more stable than the twist
boat and boat conformers. Exceptions arise when there are over-riding
circumstances.
E.g.
Bicyclo[2.2.2]octane
(E)- or trans-1,3-ditertiary-butyl
cyclohexane
(CH3)3C
1,4-bridged ring systems:
the boat has less strain
C(CH3) 3
the twist boat conformer
avoids an axial t-butyl group
2. The most stable chair conformers are those with the largest groups in
equatorial positions.
Conformational Analysis of Disubstituted Cyclohexanes
When considering the conformational isomerism of disubstituted cyclohexanes,
the fact they exist as cis and trans isomers must be taken into account, provided
the substituents are on different carbon atoms. Chirality is ignored in these
discussions.
1,2-Dimethylcyclohexane
Cis isomer
CH3 (ax)
CH3 (ax)
CH3 (eq)
CH3 (eq)
conformers are of equal stability (they are both equatorialaxial conformers), hence there is conformational "mobility"
Trans isomer
CH3 (ax)
CH3 (eq)
CH3 (eq)
CH3 (ax)
less stable diaxial
conformer (minor)
more stable diequatorial
conformer (major)
The diequatorial conformer dominates and the conformational
isomerism is effectively "locked" or "frozen"
1,3-dimethylcyclohexane
1,3- disubstitution with methyl groups leads to a similar picture to 1,2dimethylcyclohexane, but the situation regarding frozen conformational
isomerism is reversed for the cis and trans isomers:
Cis isomer
CH3
(eq)
CH3
(eq)
more stable diequatorial
conformer
CH3
(ax)
CH3
(ax)
less stable diaxial
conformer
Trans isomer
(ax)
CH3
(eq)
CH3
CH3
(eq)
CH3
(ax)
Both conformers (equatorial-axial) are of equal stability,
hence the conformational isomerism is 'mobile'
1,4-Dimethylcyclohexane
The situation for 1,4-dimethylcyclohexane is the same as that for 1,2dimethylcyclohexane.
Note, that in all the above cases, when the substituents are different, the
preferred chair conformer will be that with the larger group in an equatorial
position.
Sir Derek Barton, founder of conformational analysis
Conformations of Polycyclic Molecules
A polycyclic molecule is one that contains more than one ring system. If two ring
systems are joined at adjacent atoms and share a common bond, they are said
to be fused, as in the case of decalin (bicyclo [4.4.0] decane), with two
cyclohexane rings. Fused cycloalkane molecules like decalin are really special
cases of 1,2-disubstitution and so the conformational isomerism of decalin is
similar to that of 1,2-dimethylcyclohaxane: there are cis and trans isomers with
the following characteristics.
H
H
10
1
9
2
6
8
5
7
3
or
H
4
H
With one equatorial and
one axial C-C ring
substituent, the system
is conformationally
mobile
Cis-decalin
H
H
or
H
Trans-decalin
H
With two (favored)
equatorial C-C
substituents, the system
is conformationally
rigid
Fused ring polycyclic compounds are important in nature: steroids consist of
three fused cyclohexane rings (A, B and C) and one fused cyclopentane ring (D),
as shown for androsterone, overleaf.
CH3
CH3
B H
A
C H
O
D
H
HO
H
CH3
CH3
O
H
H
HO
Unlike fused polycyclic systems, bridged ring systems have the rings joined at
non-adjacent atoms, as illustrated by the norbornane system, which can be
considered as a cyclohexane ring bridged by a single carbon at positions 1 and 4.
The norbornane system can be drawn in three different ways:
Note this bridged system is conformationally rigid. As explained in class 6, the
systematic name for norbornane is bicyclo [2.2.1] heptane. Substituted
norbornanes occur widely in nature, a well-known example being camphor (a
terpenoid):
CH3
CH3
CH3
O