National Higher School of Technology and Engineering- Annaba
Preparatory classes of sciences and technology
Second year
University year: 2025/2026
Organic chemistry course
Chapter 2 : Stereochemistry of organic compounds
-Part 3-
Dr. A. AMIRA
Email : [Link]@[Link]
1
Type of Stereoisomers
Consider that A and B are :
Stereoisomers
Is it possible to move from A to B by simple rotations around single bonds?
Conformational Configurational
stereoisomers stereoisomers
(called also conformers or rotamers)
Conformations of Conformations of
acyclic hydrocarbons cyclic hydrocarbons
2
Conformational analysis of cyclohexane
At room temperature, the free rotation of C-C bonds leads to 1000000
Interconversions per second, but at -100°C interconversion is blocked.
Consider the energy diagram of cyclohexane represented below:
Half-chair conformation Half-chair conformation
Boat conformation
Twist boat Twist boat
Chair conformation Chair conformation
Figure 1. The potential energy diagram of cyclohexane conformations
3
Conformational analysis of cyclohexane
-Chair conformation-
This is the most stable low-energy conformation, accounting for 99% of
all conformers, and exists in two forms that interconvert by rotation of
the C-C bonds.
How to draw chair conformations?
1) Draw two offset parallel 2) Draw another pair of parallel 3) Connect with a third
bonds in the middle of the rectangle bonds from the end of the first pair parallel bonds
H H H H
H H
5H 1 4 H6
6 5
H H H H
H H H H
3 2
4 H 2 3H 1
H H
H H H H
4) Draw vertical lines with C1 (up), then 5) Draw equatorial bonds, which are parallel
alternate (down/up), there are axial bonds. to C-C bonds within the ring.
During interconversion, the axial bonds become equatorial and vice versa without changing
direction (up, down). 4
Conformational analysis of cyclohexane
-Project chair conformation in Newman -
In Newman projection, the stability of the conformer is better justified, as all the bonds are
staggered.
H H
H H H
5 H H
1 6 1 2 H
6 H
H H
HH
H H 5 3
3 H H
4 4
H 2
H H H H
H H
In chair conformations, the axial bonds are very close together, unlike the equatorial bonds,
which are very far apart.
5
Conformational analysis of cyclohexane
-Boat conformation-
Boat conformation is one of the transition states between the two chair
conformations, and steric strain is remarkable in the Newman projection, it is
unstable eclipsed conformation.
6
1,3-diaxial interactions in chair conformation
When cyclohexane is substituted in axial position, the atom or group causes significant
steric strain. Resulting interactions, called 1,3-diaxial interactions (1,3-DI), responsible
for the energy and stability that each chair conformation possesses.
mono-substituted cyclohexane:
di-substituted cyclohexane:
7
mono-substituted cyclohexane
The conformational equilibrium is shifted towards the most stable conformation, which
has no diaxial interaction and for which the substituent is in the equatorial position.
methylcyclohexane:
tert-butylcyclohexane:
chlorocyclohexane:
The population of the most stable conformer is always in the majority and varies according
to the nature of the substituent. 8
di-substituted cyclohexane
-cis/trans isomerism-
cis trans
(The two substituents are (The two substituents are
on the same side of the ring) on opposite sides of the ring)
cis-1-ethyl-3-methylcyclohexane:
Wedge in Cram
Use the same direction for (is UP in chair conformation)
numbering the ring, in accordance
with IUPAC rules, in preference. Dash in Cram
(is DOWN in chair conformation)
9
di-substituted cyclohexane
-cis/trans isomerism-
cis trans
(The two substituents are (The two substituents are
on the same side of the ring) on opposite sides of the ring)
trans-1-ethyl-3-methylcyclohexane:
10
di-substituted cyclohexane
-Energy cost-
When the two chair conformers have the same number of diaxial interactions:
Put the substituent having the highest energy cost in the equatorial position.
The table below shows the energy cost of 1,3-diaxial interactions for various substituents.
Table 1. Energy cost of 1,3-diaxial interactions for several common substituents
Substituant X Energy cost( kJ/mol)
−𝐶𝐻3 7.6
−𝐶𝐻2 𝐶𝐻3 8.0
−𝐶𝐻(𝐶𝐻3)2 9.2
−𝐶(𝐶𝐻3)3 22.8
−𝐶𝑙 2.0
−𝑂𝐻 4.2
−𝑁𝐻2 5.9
11
Comparing stability of chair conformation
Application 1:
Complete the equilibrium for the following compounds, identify the more stable
Conformation.
cis-cyclohexane-1,3-diol:
A stabilizing intramolecular
hydrogen bond
1,4-dichloro-2-ethylcyclohexane:
(8.0 kJ/mol)
(2.0 kJ/mol) The lowest total
energy cost= 4.0 kJ/mol
(2.0 kJ/mol)
2 ID-1,3
4 ID-1,3
12
Relationship between cyclohexane derivatives
Application 2: For each pair of the following compounds, identify the relationship of
isomerism.
13
Relationship between cyclohexane compounds
Solution:
14