Stereochemistry of Cyclohexane

Stereochemistry of Cyclohexane

Session Objectives

By the end of this
session, students will be able to:

• Explain Ring inversion of cyclohexane

• Discuss factors effecting mono and disubstitution of
cyclohexane with examples

Drawing Cyclohexane

• In the structure of cyclohexane, all the six carbons are
identical but there are two types of hydrogens

• One type stick either vertically up or down are called
axial hydrogen atoms

• Others stick out sideways are called equatorial hydrogen
atoms

• Each carbon is attached to two hydrogens, one in axial and
other in equatorial positions

Drawing Cyclohexane

Ring inversion or flipping of cyclohexane

• Chair conformer is the preferred conformation for
cyclohexane

13CNMR shows single signal showing that all six
carbons are same

• But there are two different sorts of protons- axial and
equatorial. Still 1HNMR shows only one signal

• In monosubstituted cyclohexane, there should be two
isomers detectable one with axial and the other with equatorial

Ring inversion or flipping of cyclohexane

• But at room temperature again one signal is seen

• This gives us a clue that two isomers are conformers and
interconvert rapidly at room temperature called as ring inversion or flip

• After ring inversion, all the bonds in axial changes to
equatorial and vice versa

Ring inversion process

• The whole inversion process can be broken down into
conformations shown below

• The green arrows show the direction in which the
individual carbon atoms should move in order to get to the next conformation

Ring inversion process

Energy profile for ring inversion of cyclohexane

• Shows that half-chair is the energy maximum in the
conversion of chair to twist boat

• True boat conformation is the energy maximum on
interchanging between two mirror image twist boat conformers

• The second twist boat is converted to other chair
conformation through another half-chair

• This clearly shows that ring inversion interconverts the
axial and equatorial protons too fast for them to be detected by NMR

• Exchanging occurs at a rate of 2 x 105 s-1
at 25 0C

Energy profile for ring inversion of cyclohexane

Substituted cyclohexane- mono

• Cyclohexane is free of angle strain, torsional strain and
van der waals strain

• In monosubstitution, there can exist two different chair
conformers- one with axial and other with equatorial

• Both will be in equilibrium, but of different energies
with axial substituent in higher energy (7.3 KJ mol-1 higher than
equatorial)

• In cyclohexane, a given atom or group has more room in an
equatorial position than in an axial position

Substituted cyclohexane- mono

• Why axial is higher in energy than equatorial conformer?

1) axial conformer is destabilized by repulsion between the
axial group X and two axial hydrogen atoms on the same side of the ring known
1,3-diaxial interaction. Increases with X gets larger

2) In the equatorial conformer the C–X bond is
anti-periplanar to two C–C bonds, while, for the axial conformer, the C–X bond
is synclinal (gauche) to two C–C bonds

Substituted cyclohexane- mono

• The amount of equatorial conformer present does increase
in the order Me < Et < i-Pr < t-Bu

• The equilibrium constant does not depend on the actual
size of the substituent, but rather its interaction with the neighbouring axial
hydrogens

• In the case of the methoxy group, the oxygen acts as link
and removes the methyl group away from the ring, lessening the interaction-
methoxy group prefers axial

Substituted cyclohexane- mono

What happens with more than one substitution on the ring?

• When there are two or more substituents on the ring,
stereoisomerism is possible

• For example, 1,4-cyclohexanediol, two isomers are
possible- cis isomer (both the substituents are either above or below ring),
trans isomer (one is above and other is below)

• For a cis-1,4-disubstituted cyclohexane with both
the substituents same, ring inversion leads to a second identical conformation

• For the trans configuration there is one
conformation with both groups axial and one with both groups equatorial

Disubstitution on cyclohexane

Disubstitution on cyclohexane

Summary

• Chair conformer is the preferred conformation for
cyclohexane

• Ring inversion interconverts the axial and equatorial
protons too fast for them to be detected by NMR

• Cyclohexane is free of angle strain, torsional strain and
van der waals strain

• In the disubstitution of cyclohexane, we need to consider
the following factors:

1) Position isomerism

2) Stereoisomerism which includes geometrical and optical

3) Relative sizes of the two substituents

4) Nature of the substituents

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