KISII UNIVERSITY

DEPARTMET OF CHEMISTRY
UNIT: ORGANIC STEREOCHEMISTRY AND REACTION
MECHANISMS.
UNIT CODE: CHEM 436

COURSE CONTENT

Introduction to stereochemistry isomerism

 definitions
 types of stereomers
 torsional strain and dihedral angle

Dynamic stereochemistry: - conformations and stability.

 conformational analysis of cyclohexane
 energy profile of chair to chair conversions
 Monosubstituted cyclohexane – equatorial and axial groups,
relative stabilities and effect on reaction rates.
Concerted reactions and HOMO-LUMO frontier orbital theory

Pericyclic reactions: -Cycloaddition reactions - suprafacial and antarafacial

-Electrocyclic reactions -conrotatory and disrotatory modes.
-Allowed and disallowed reactions

Carbonium ions: -classical and non-classical carbonium ions

Photochemistry
Conformational Analysis of Cycloalkanes

TABLE OF CONTENTS
1. Learning Outcomes
2. Introduction
3. Baeyer strain Theory
4. Conformational Analysis of Cycloalkanes
4.1. Cyclopropane
4.2. Cyclobutane
4.3. Cyclopentane
4.4. Cyclohexane
4.5. Monosubstituted cyclohexane

1. Learning Outcomes
After studying this topic, you shall be able to :
 Know about three dimensional structures of alicyclic compounds.
 Learn about the concept of Conformation.
 Understand Baeyer strain theory for predicting stability of ring compounds and its
incorrectness.
 Identify different types of strains in conformations of Cycloalkanes.
 Draw energy profile diagrams for various conformations of cyclohexane.
 Preferred configuration of substituted cyclohexanes.

2. Introduction
Three Dimensional Shapes of Organic Molecules

We live in a three dimensional world and the same is true for molecules! Molecules are three
dimensional entities with well-defined shapes and structures. Though most of the time we see
their 2D drawings in books, it is always a challenge to visualize their 3D shapes without the help
of models. The study of stereochemistry of organic molecules allows us to visualize and draw
these molecules in a better way and also to analyze and predict their behavior in 3-D space. The
shapes of organic molecules depends on the type of bonds – single, double or triple. While the
single bonds imparts flexibility, the double and triple bonds imparts rigidity in the molecules.
The free rotation around C-C single bond gives rise to conformations that are interconvertible
without breaking any bond. And the restricted rotation around a double bond gives rise to
configurations or geometrical isomers which are not interconvertible unless a bond is broken.
The free rotation around all single bonds within a same molecule can give rise to various
different shapes of the molecule.

Note : the arrangement around the double bond is never disturbed as their rotation is restricted!
The different shapes that a molecule can adopt due to rotation about single bonds are called
conformations. Since the single bonds can be rotated to any fractional amount of a degree, giving rise to
a new conformation minutely different from the other, conformations are infinite in number and hence are
called conformers instead of stereo-isomers, The term rotational isomers is also used often. The study
of molecular conformations and their relative energies is called Conformational Analysis.
Conformational analysis allows us to relate the shapes of molecules with their chemical reactivity and
physical properties.

3. Baeyer Strain Theory

The theory proposed by Adolf von Bayer in 1885, popularly known as Bayer Strain theory, suggested that
the angle strain in cycloalkanes increases proportionally as the deviation from regular tetrahedron
geometry increases. Hence, a cyclopentane ring with an internal angle 108° would be most stable (as it
has minimum deviation from a regular tetrahedral angle of

However, it was soon realized that cycloalkanes (except cyclopropane) are not planar
compounds and the theory was not correct except for very small rings. Cycloalkanes can bend
and twist about their C-C single bonds to acquire stability. Infact, a puckered structure of
cyclohexane has a zero angle strain! (Fig. 3)

One can compare the stabilities of cycloalkanes by using their heats of combustion data.
Minimum value of heats of combustion suggests maximum stability. According to this data,
cyclo propane has a maximum strain and is least stable while cyclohexane has the least strain
and is most stable.
4. Conformations of Cycloalkanes
Molecules show strain arising out of non-ideal geometry. The internal energy of the molecule is
dependent on several factors. These are
Total strain energy = 1 + 2 + 3 + 4
1 = stretching and compression of bonds (bond strain)
2 = Bond angle distortion (Baeyer strain, classical strain)
3 = Tortional strain (eclipsing strain)
4 = steric strain (vander waals strain)
A molecule will adopt the geometry, that minimises its total strain energy. The method of calculation of
total strain energy is spoken as molecular mechanics.
Steric strain: Any type of repulsion between two closely spaced non-bonded atoms or group of atoms is
termed as steric strain. The repulsions between electrons of these closely spaced atoms imparts a
destabilising effect and is the major cause of the overall strain in a molecule. It can be classified into
various types of strains as described below.
Angle strain: If the angle between a pair of adjacent bonds on a carbon atom is less than the tetrahedral
angle (i.e., 109.5o) then there is a destabilisation due to the bond pair - bond pair repulsion.
Figure 5. Angle strain
Van der Waals strain: This type of strain arises when the electron clouds of a pair of bulky groups are
too close to each other. It leads to an increase in energy of the system due to the electrostatic repulsion of
the electron clouds.

Torsional strain: When a molecule is able to rotate around a sigma bond, the other three
bonds on each carbon holding the single bond move relative to each other resulting in different
levels of torsional strain. The relative movement of these bonds can be better understood in
terms of dihedral angle. A dihedral angle (θ) is the angle between the two intersecting planes
formed by the bonds on adjacent carbon atoms (figure 7). The maximum strain is observed
when these bonds are closest to each other, i.e. in an eclipsing position (θ = 0°). Hence this
strain is also known as eclipsing strain. With the rotation around the sigma bond, the dihedral
angle changes and consequently the repulsion between the bonded pair of electrons (torsional
strain) also changes. The strain is minimum at θ = 60° (staggered conformation).
Figure 7. Torsional strain and torsional angle
Ring strain: Generally, a ring or cyclic structure is less stable than an equivalent acyclic structure,
primarily due to angle and torsional strain. The extra energy is released when the ring is opened is known
as ring strain.
Let us now look at the conformations of specific cycloalkanes and their respective stabilities in detail.
Conformations of small rings
Cyclopropane
The three carbons in cyclopropane should lie in a plane as any three points describe a plane. All the C-C
bond lengths in propane are same which suggests that all the three carbons must lie at the corners of an
equilateral triangle. In this geometry, the deviation from the regular tetrahedral angle is the maximum
(from normal tetrahedral angle of 109.5° to 60°) and hence there is extensive strain in the cyclopropane
ring. This is evident from the large heat of combustion value per methyl group. Infact the C-C bonds in
cyclopropane are bent in order to form an equilateral triangle. Further strain is imparted by eclipsing
interactions as all the C-H bonds in cyclopropane are eclipsed. And C-C bond rotation to relieve this
strain is not possible due to the rigidity of the ring. Hence cyclopropane is considerably strained molecule
and readily undergoes reactions involving ring opening.

Figure 8. Planar conformation of cyclopropane: All the bonds are eclipsed

Figure 9. Orbital overlap in cyclohexane showing bent bonds

Cyclobutane

In cyclobutane, the ring adopts a puckered or wing-shaped conformation. Though the distortion from the
planar structure reduces the torsional strain (eclipsed bonds move slightly away), it increases the angle
strain (angle decreases as the ring puckers). A balance between the two is struck when the ring puckers to
about 34° (i.e. when one methylene moves 34° up or below the rest of the three carbon forming a plane).
The planar form of cyclobutane (where all the bonds are eclipsed) is just 1.4 kcal/mol more in energy than
the puckered conformation.
Figure 10. Puckered conformation of cyclobutane

Cyclopentane
Unlike what was predicted by Baeyer, cyclopentane is not entirely strain free even though in a planar
conformation the C-C-C bond angles are close to 109.5°. The eclipsed bonds in the planar cyclobutane
impart considerable torsional strain forcing it to attain a more stable puckered conformation. The heat of
combustion data indicates the total strain in the ring. On distorting the planarity, cyclopentane partly
relieves the torsional strain but increases the angle strain (similar to cyclobutane). The minimum energy
conformation is thus adopted by balancing the two opposing effects. There are two conformations of
comparable energy, the ‘open envelope’ (with four carbon atoms in a plane and one above or below it)
and the ‘twist form’ (with three carbon atoms in a plane and two above or below it). The atoms in the ring
rapidly take turns not to be in the plane and cyclopentanes have much less well defined conformational
properties than cyclohexanes.

Figure 11. Open envelope conformation of cyclopentane

Conformational Analysis of Cyclohexane
As predicted by heats of combustion, cyclohexane is strain free ring. It has neither angle strain nor
torsional strain in its chair conformation. This is because it can pucker in such a way that all of the bonds
are perfectly staggered, and in this conformation all of the bonds are 109°. In the chair conformation, four
carbons lie in a plane while two lie above and below this plane. There are two types of C-H bonds in
cyclohexane. The vertical bonds parallel to the axis are called axial bonds. The near horizontal
bonds radiating away from the equator are called equatorial bonds. They are slanting up and
slanting down alternatively.
Figure 12. Chair conformation of cyclohexane; axial and equatorial bonds in chair conformation
All six axial C-H bonds are anti to each other and skew or gauche to equatorial C-H bonds and also to
ring skeletal bonds as shown in the Newman projection of chair conformation of cyclohexane figure 13.
Figure 13. Newman projection of chair conformation of cyclohexane showing gauche interaction; cis and
trans relationship of axial and equatorial bonds
Note that any pair of axial and equatorial bonds on adjacent carbon atoms are cis to each other (i.e. they
point in the same direction, either up or down) and any pair of axial-axial or equatorial-equatorial bonds
on adjacent carbon atoms are trans (or anti) to each other.
Cyclohexane theoretically can exist in two different chair conformations as shown in figure and the two
forms can interconvert easily through ring flipping as shown in the figure 14. Ring flipping is nothing but
a rotation of single bonds in the molecule. An interesting point to note in this interconversion is that all
the axial bonds in ring 1 (chair) become equatorial bonds in ring 2 (inverted chair) and vice versa.

Figure 14. Ring flip in cyclohexane: interconversion of chair and inverted chair conformations

There are other infinite conformations of cyclohexane of varying energies besides chair conformation due
to the rotation around single bonds. Some of them with special names are boat, twist boat and half chair
conformations (ones representing the peaks and valleys in the energy diagram of cyclohexane
conformations) as shown in figure 15.
Figure 15. Energy Diagram of various conformations of cyclohexane
From the figure we can see that chair conformation has the minimum energy out of all the possible
conformations and is therefore called the ground state conformation of cyclohexane. The boat
conformation is 6.9 kcal/mol higher in energy than the chair conformation. This may largely be attributed
to torsional strain among the four pairs of hydrogens and to some extent to the flagpole interactions
between the hydrogens on the diagonally opposite carbons (figure 16). In twist boat conformation, the
planarity of the four carbons (as in boat) is distorted or twisted and hence thename ‘twist boat’. By
twisting the planar carbons, the strain due to eclipsed bonds (in boat) is somewhat relieved. The
twist boat conformation is only 0.4 kcal/mol more stable than the boat conformation. In fact, boat
conformation is the transition state in moving from one twist boat to another. Likewise the two
half chair conformations (represented by the highest energy peaks) are the transition states in
the interconversion of one chair form to another. Table 1 summarizes the amount and types of
strain in various conformations of cyclohexane.
Figure 16. Boat, twist boat and half chair conformations of cyclohexane
Table 1. Types Angle strain Torsional strain Van der Waals Flagpole strain
of strain in strain
various
conformations
of cyclohexane

× × × ×
Conformation
Chair
 × √ √ √
√ (slight) √(slight) √(slight) ×
Boat

√ √ √ ×
Twist boat
Half chair

possibilities we have are: either methyl group occupies axial position or it occupies equatorial position.
The two can interchange through ring flipping as shown in figure 17.

Figure 17. Chair conformations of methylcyclohexane showing axial and equatorial methyl group
Which of the two is more stable? If we draw Newman projection for methylcyclohexane, we will see that
the axial methylcyclohexane experiences gauche interactions between the methyl group and ring
methylene (figure 18) while equatorial methylcyclohexane has no such interactions and hence has
somewhat lesser energy than the axial methylcyclohexane. Besides gauch interactions, axial methyl group
experience steric repulsions from the nearby axial hydrogens which further increases the energy of axial
methylcyclohexane. These steric interactions between the substituent in axial position at C-1 and the axial
hydrogens at C-3 are called 1,3-diaxial interactions (figure 17). When the methyl group is at equatorial
position, there are no significant gauche interactions as methyl group is anti to ring C-C bond. There are
no diaxial interactions as well and hence equatorial conformation becomes more stable than the axial. The
equatorial conformation is favored in the equilibrium because the axial isomer has about 1.8 kcal/mol of
steric strain. This observation can be generalized to all the substituents, if present at the equatorial
position will always be more stable than at the axial position.
Figure 18. Newman projection of chair conformations of methylcyclohexane showing axial and equatorial
methyl group
5. Summary
 Stereochemistry is the study of 3D structures and shapes of organic molecules. It allows
us to visualize, draw and understand these molecules in a better way and also to analyze
and predict their behavior in 3-D space.
 The different shapes that a molecule can assume due to rotation about single bonds are
called conformations. The study of molecular conformations and their relative energies
is called Conformational Analysis.
 The stabilities of cycloalkanes can be compared by using their heats of combustion data.
Minimum value of heats of combustion suggests maximum stability. A puckered
structure of cyclohexane has a zero angle strain!
 Various types of strain that we need to be familiar with while working with cycloalkanes
are: angle strain, torsional strain, and van der Waals strain.
 Cyclopropane is considerably strained molecule with all the atoms in a plane and all C-H
bonds completely eclipsed with no possibility of rotation around C-C single bonds.
 Cyclobutane, the ring adopts a puckered or wing-shaped conformation to relieve torsional
strain but in doing so acquires angle strain.
 Cyclopentane adopts either an open envelope or a twist conformation and keep changing
the envelope flap around the ring generating five possible puckered conformers and thus
have less well defined conformational properties.
 Cyclohexane, in chair conformation is strain free as all the C-H bonds are anti to each
other and there is no angle strain. It can have two chair conformations (chair and inverted
chair) which can interconvert by ring flipping. Ring flipping changes all the equatorial
bonds to axial and axial bonds to equatorial.
 Other significant conformations of cyclohexane boat, twist boat and half chair
conformations. The relative energies of these conformations are : Chair < twist boat <
boat < half chair.
 The boat conformation possess torsional strain due eclipsing of four C-H bonds and
flagpole interactions. It is 6.9 kcal/mol more than the chair conformation.
 Twist boat and half chair are more in energy than the chair conformation by 5.5 kcal/mol
and 10 kcal/mol respectively.
 Monosubtitution in cyclohexane prefers equatorial position which is free from gauch or
steric strain as compared to axial position which is energetically destabilized due to
gauch and 1,3-diaxial interactions. One axial substitution roughly costs 1.8 kcal/mol of
energy.