STEREOCHEMISTRY OF DISUBSTITUTED

CYCLOHEXANE
CH3 CH3
CH3

CH3

CH3 CH3
5

6 1 CH3

3
4
2
CH3
 Stereochemistry
Stereochemistry is the branch of chemistry deals with study of
three dimensional structures of organic compounds.
HO CH3
Chiral Carbon: Carbon atom to which four different
*
atoms/ groups are attached. H3C Br
Geometrical Isomerism: Cis and trans CH3 Chiral carbon
CH3
5

6 1

3
CH3
4
2 CH3
Cis Isomer Trans Isomer
 Stereochemistry
Optical isomerism: Compound that rotates the plane of plane
polarized light is said to be optically active compound.
Dextrorotatory (+) : Rotates the plane of plane polarized light in
clockwise direction (d)
Levorotatory (+) : Rotates the plane of plane polarized light in
anticlockwise direction (l)
 Stereochemistry
CH3
CH3
Stereoisomers: They have
same molecular formula, same
bonding connectivity but different
orientation of atoms/groups in CH3
CH3
space.
COOH COOH
Enantiomers: A chiral molecule/
object has a non superimposable
H OH HO H
mirror image. CH3
H3C

Diastereomers: Stereoisomers which are not

enantiomers are called as diastereomers.
 Disubstituted Cyclohexane

In disubstituted cyclohexane two hydrogen atoms of cyclohexane molecule are

replaced by two other atoms or groups.
Depending upon relative position of two substituents following isomers are
possible
CH3

H3C CH3 CH3

CH3
CH3

CH3 CH3

1,1 1,2 1,3 1,4

disubstituted disubstituted disubstituted disubstituted
 Axial and Equatorial Hydrogen

Axial Hydrogens: Hydrogen atoms perpendicular to the ring in the chair configuration.
Equatorial Hydrogens: Hydrogen atoms present in the general plane of the molecule,
around the equator.

H H

H
H
H
H H

H H H
H
H

Axial Hydrogens Equatorial Hydrogens

 Cis and Trans Isomers of Cyclohexane
• Cis Isomer: In cis isomer both substituents are present on the same side of the
general plane of molecule
• Trans Isomer: In trans isomer one substituent is present above the general plane of
molecule while other substituent present below the plane.

Cis Isomer Trans Isomer

Ring Flip: Conversion of one chair conformation of cyclohexane into another chair
conformation by rotation around carbon-carbon single bond.
On ring flipping axial substituents become equatorial,
. and equatorial substituents
become axial.
 1,1-Disubstituted Cyclohexane

Both substituents are present on same carbon atom.

Optical Isomerism: 1,1-dimethyl cyclohexane posses plane of symmetry
(passing through C1 and C4),hence optical isomerism is not possible
Geometrical isomerism: No geometrical isomerism as both substituents are
present on same carbon atom.

CH3
5

6 1 CH3

3
4
2
 1,1-Disubstituted Cyclohexane
Conformational isomerism: Two distinct chair conformations are possible for 1,1-
disubstituted cyclohexane.
Ring flipping of conformation A produce conformation B.
In conformation A substituent R1 is axial while substituent R2 is equatorial, On ring
flipping axial substituent become equatorial and equatorial substituent become
axial
1
R
5 6
4
2
6 1 R 5 1
R
3 2
4 1
2
A 2 3 B R

When R1 and R2 are same , then A and B are also same

 1,1-Disubstituted Cyclohexane
• Relative Stability: Stability of conformation is depends upon the size of
the substituent.
• The conformation in which larger( bulkier) group is present at equatorial
position is more stable.
• Example- 1-ethyl,1-methyl cyclohexane

CH3 6
5 4
CH3 5
6 1 CH3
2
3 1
4
3 B CH3
A 2

Conformation A is more stable than conformation B

1,2-Disubstituted Cyclohexane [Cis isomer (a, e form)]
Cis 1,2 dimethyl cyclohexane
Cis isomer: Both substituents are on the same side of general plane of the molecule.
Optical Isomerism: There is no element of symmetry, thus molecule is expected to be
optically active but it is optically inactive.
Conformation 1 and 3 are non
CH3
CH3
5
superimposable mirror images of each
5
other (Enantiomer). Similarly
6 1 1 6
Conformation 2 and 4 are also
3 3 enantiomer. Flipping of conformation 1
CH3 H3C
4 4
3 produce conformation 2 having equal
1 2 2
stability, similarly flipping of 3 produce
conformation 4 with same stability. Thus
6
CH3 H3C
6 two conformations are interconverted
4
5 5 4
rapidly to each other via ring flipping at
2 CH3 H3C 2 normal temperatures and exist in equal
proportions. Thus molecule exist as a
3 2 1 1 4 3
racemic mixture.
 Cis 1,2-Dimethyl Cyclohexane
Cis isomer (a,e form), Relative Stability

H CH3
5
H
6 1

3
CH3
4
2

In Cis-1,2- Dimethyl cyclohexene, axial methyl group have two CH3-H, 1,3- diaxial
interactions and one butane gauche interaction between two methyl groups. Thus
total strain is 2.7 kcal/mole
One gauche Interaction (0.9 kcal/mole) +Two CH3-H diaxial interaction (1.8
kcal/mole) = 2.7 kcal/mole
 1,2-Disubstituted Cyclohexane
A) Trans 1,2 dimethyl cyclohexane (e, e or a, a form)
Trans isomer: Substituents are on the opposite side of general plane of molecule.
Optical Isomerism: There is no element of symmetry, thus as expected molecule is
optically active.
5 5 As expected trans 1,2
6 1 CH3 H3C
1 6 dimethyl cyclohexane exist in
3
CH3 H3C
3 pair of enantiomers 1 and 3 or
4 4
3 2 and 4. Conformation 1 on
1 2 2
ring flipping produce less
stable diaxial conformation 2.
CH3 H3C
6 6 Conformation 1 and 2 or 3
4
5 5 4 and 4 are diastereomers of
2 2
1
each other
1
3 2 4 3
CH3 CH3
 1,2-Dimethyl Cyclohexane
Trans isomer, Relative stability
H CH3
5 5
H
6 1 6 1
CH3

3 3
CH3
4 4
H 2 2
H
H3C

In trans 1,2- Dimethyl cyclohexene (diaxial form), each axial methyl groups have two
CH3-H, 1,3- diaxial interactions. Thus total 4 such interactions contribute 0.9 x 4=3.6
kcal/mole strain
In trans 1,2- Dimethyl cyclohexene (diequatorial form), There is one butane gauche
interaction between two methyl groups. Thus total energy of molecule is 0.9 kcal/mole
 Stability order
1,2-Disubstituted Cyclohexane

Trans (e, e ) Cis (a, e )

0.9 kcal /mole 2.7 kcal /mole Trans (a, a )
3.6 kcal /mole
 1,3-Disubstituted Cyclohexane
Cis 1,3 dimethyl cyclohexane (a, a or e, e form)

Conformation 1
and 3 as well as 2
and 4 are non
super imposable
mirror images of
each other
(enantiomers)
 1,3-Disubstituted Cyclohexane
Cis 1,3 dimethyl cyclohexane (a, a or e, e form)
Optical Isomerism: Cis 1,3 dimethyl cyclohexane possess a plane of symmetry (
Passing through C2 and C5 ) Hence it is meso compound and is optically inactive

Plane of Symmetry
passing through C2
and C5 can easily
seen in Newman’s
structure
 1,3-Disubstituted Cyclohexane
Cis isomer, Relative stability
In cis 1,3- Dimethyl cyclohexene (diaxial form), each axial methyl groups have two
butane gauche interactions.
(Methyl group at C1 is gauche to C3 and C5 carbon of the ring and methyl group at
C3 is gauche to C1 and C5 carbon of the ring )
These four interactions contributes 3.6 kcal/mole energy.
In addition to this there is one interaction between two CH3 groups which
contribute 1.8 kcal/mole.
Thus total strain is 3.6 + 1.8 = 5.4 kcal/mole.
In diequatorial form (e.e), there is no such interaction, hence strain is 0 kcal/mole
 1,3-Disubstituted Cyclohexane
Trans isomer (a,e form)
Optical Isomerism: In trans 1,3 dimethyl cyclohexane there is no plane of
symmetry. Hence molecule is expected to be optically active.

Conformation 1 and 3 as
well as 3 and 4 are non
super imposable mirror
images of each other
(enantiomers). Ring
flipping produce identical
compounds and have
equal energy.
1,3-Disubstituted Cyclohexane
Trans isomer, Relative stability

In trans 1,3- Dimethyl cyclohexene, axial

methyl groups have two CH3-H, 1,3 diaxil
interaction. These two interactions
contributes 1.8 kcal/mole energy. 0.9 +
0.9 = 1.8 kcal/mole.

Stability order Cis 1,3 (e, e) 0 kcal/mole >

Trans 1,3 (a, e) 1.8 kcal/mole > Cis 1,3(a,
a) 5.4kcal/mole
 1,4-Disubstituted Cyclohexane
Cis isomer (a,e form)
Optical Isomerism: Cis 1,4 dimethyl cyclohexane possess a plane of symmetry ( Passing
through C1 and C4 ) Hence it is optically inactive and exist in meso form.

Conformation 1 and 2
as well as 3 and 4
are superimposable.
 1,4-Disubstituted Cyclohexane
Cis isomer, Relative stability

In Cis 1,4- Dimethyl cyclohexene, axial methyl group have two CH3-H, 1,3 diaxial
interaction. These two interactions contributes 1.8 kcal/mole energy. Other methyl
group present at equatorial position have no interaction. Thus total strain is 0.9 +
0.9 = 1.8 kcal/mole.
 1,4-Disubstituted Cyclohexane
Trans isomer (a, a or e, e form)
Optical Isomerism: Trans 1,4 dimethyl cyclohexane possess a plane of symmetry ( Passing
through C1 and C4 ) and also Centre of symmetry. Hence it is optically inactive.

Ring flipping of
diequatorial form
produce less
stable diaxial form
 1,4-Disubstituted Cyclohexane
Trans isomer, Relative stability

In trans 1,4- Dimethyl cyclohexene diaxial form, Each axial methyl group have two
CH3-H, 1,3 diaxial interaction. These four interactions contributes 3.6 kcal/mole
energy. Diequatorial form is more stable and have 0 kcal/mole strain

Stability order: Trans 1,4 (e, e) 0kcal/mole > Cis 1,4(a, e) 1.8kcal/mole > Trans 1,4 (a, a)
3.6 kcal/mole
Conformations and energies of dimethyl
cyclohexane
 Conformations of Decalin and their stability

➢ Saturated analogue of naphthalene

➢ Can be prepared by catalytic hydrogenation of naphthalene in fused
➢ It is also known as bicyclo[4,4,0]decane
 Conformations of Decalin and their stability

➢ Decalin is numbered like naphthalene where ring junction known as bridgehead

and get number 9 and 10

➢ If one of the six membered ring of decalin is viewed as an independent

cyclohexane ring then it appear like 1,2 disubstituted cyclohexane
 Conformations of Decalin and their stability

➢ Stereochemistry of decalin can be understood as similar to that of 1,2

disubstituted cyclohexane.

➢ In cis isomer both C9 and C10 hydrogens are present either upward or
downward
Conformations of Decalin and their stability

➢ In cis isomer both

C9 and C10
hydrogens are
present either
upward or
downward
 Conformations of Decalin and their stability
➢ In trans isomer one hydrogen ( either C9 or C10) is present above the plane
(upward) while other present below the plane (downward)
➢ Similar to trans 1,2 dimethyl cyclohexane, two orientation of methylene group of
ring B are expected ( i.e e, e and a ,a)
➢ Formation of ring B in diaxial form is not possible hence this conformation does
not exist and trans decalin exist as diequatorial form
Conformations of Decalin and their stability

➢ In cis isomer there are

three butane gauche
interactions Hence
total energy is 0.9 x 3
= 2.7 kcal/mole

➢ In trans isomer there

is no butane gauche
interaction. Hence
total energy is 0
kcal/mole
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