Stereochemistry-

Conformational Analysis of cyclic and

acyclic compounds

References
1. Stereochemistry of organic compounds, Ernest L Eliel, Samuel H.Wilen, A Wliley Inter Science
publication 2004
2. F.A.Carey and R.J. Sundberg, Advanced Organic Chemistry, Part A and Part B, 5th edition, Springer,
New York (2007).
3. P.S.Kalsi Stereochemistry And Mechanism (Through Solved Problems), New Age International, New
Delhi,2007
 Sigma bonds and bond rotation
Groups bonded only by a sigma bond can undergo
rotation about that bond with respect to each other.
The temporary molecular shapes that result from
rotations of groups about single bonds are called
conformation of the molecule.

An analysis of the energy changes that a molecule undergoes as

groups rotate about single bonds is called a conformational analysis.
 Conformations of Acyclic Alkanes

Conformations are different arrangements of atoms that are

interconverted by rotation about single bonds.

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• Names are given to two different conformations.
• In the eclipsed conformation, the C—H bonds on one
carbon are directly aligned with the C—H bonds on the
adjacent carbon.
• In the staggered conformation, the C—H bonds on one
carbon bisect the H—C—H bond angle on the adjacent
carbon.

4
• Rotating the atoms on one carbon by 60° converts an eclipsed
conformation into a staggered conformation, and vice versa.
• The angle that separates a bond on one atom from a bond on an
adjacent atom is called a dihedral angle. For ethane in the staggered
conformation, the dihedral angle for the C—H bonds is 60°. For eclipsed
ethane, it is 0°.

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Let us consider the ethane molecule as an example

H
H
H
The staggered conformation of ethane
H
H ÒÒÍéµÄ½»²æʽ¹¹Ïó
H

H
H The eclipsed conformation of ethane
H
ÒÒÍéµÄÖصþʽ¹¹Ïó
H
H
H
Ethane
（Sawhorse formula)
 Newman Projection formula

H
H
H H H
H
The staggered conformation of ethane
H
H H H ÒÒÍéµÄ½»²æʽ¹¹Ïó
H
H

H H H
H
H
H The eclipsed conformation of ethane
H
H H H ÒÒÍéµÄÖصþʽ¹¹Ïó
H H

Newman projection formula

 Newman Projection formula

H
H H The bonds of the front carbon atom
are represented (ǰ̼£©
H H
H

H H Those of the back atom are represented

(ºó̼)
H
H H
H

Newman projection formula

Let us consider the ethane molecule as an example
 Conformational Analysis
Drawing Acyclic Molecules

• Sawhorse Drawings
• The staggered and eclipsed conformations of ethane interconvert at room
temperature, but each conformer is not equally stable.
• The staggered conformations are more stable (lower in energy) than the
eclipsed conformations.
• Electron-electron repulsion between bonds in the eclipsed conformation
increases its energy compared with the staggered conformation, where
the bonding electrons are farther apart.

13
Individual molecule is likely to be in the staggered conformation
at any given instant, but each molecule can rapidly traverse
through the eclipsed conformation. The rate of rotation is about
6×109 s−1 at 250C

Vander Waals repulsions are a major factor in conformational

preferences and energy barriers for ethane

The barrier to rotation is called the torsional barrier

The main factor responsible for the torsional barrier is σ - σ ∗

delocalization (hyperconjugation), which favors the staggered
conformation.
 Different Conformations of Ethane

• A staggered conformer is more stable than an eclipsed

conformer
• Torsional strain: repulsion between pairs of bonding
electrons
• The difference in energy between staggered and eclipsed conformers is ~3
kcal/mol, with each eclipsed C—H bond contributing 1 kcal/mol. The energy
difference between staggered and eclipsed conformers is called torsional energy.
• Torsional strain is an increase in energy caused by eclipsing interactions.

Graph: Energy versus dihedral angle for ethane

16
 Discussion
In ethane the difference in energy between the
staggered and eclipsed conformation is 2.8 kcal mol-1
(12 KJ mol-1). This small barrier to rotation is called
the torsion barrier of the single bond . Unless the
temperature is extremely low (-250 oC) many ethane
molecules will have enough energy to surmount this
barrier.
Newman projections for the staggered and eclipsed
conformations of propane

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Conformational analysis of butane

If we consider rotation about the C2-C3 bond of butane,

torsional strain plays a part, too.

C4H10

H H H H H H
H C C C C H CH3 C C CH3

H H H H H H
Conformation of Butane
• The energy difference between the lowest and highest energy conformations is
called a barrier to rotation.
• Since the lowest energy conformation has all bonds staggered and all large
groups anti, alkanes are often drawn in zigzag skeletal structures to indicate
this.

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 Relationship to Gauche Butane
Interactions
• Gauche butane is less stable than anti butane by 3.8 kJ/mol because of
steric interference between hydrogen atoms on the two methyl groups
• The four-carbon fragment of axial methylcyclohexane and gauche butane
have the same steric interaction
• In general, equatorial positions give more stable isomer
Six different conformations of butane

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We should look at the important conformations of butane

Anti An Eclipsed

gauche An eclipsed
• A staggered conformation with two larger groups 180° from each
other is called anti.
• A staggered conformation with two larger groups 60° from each
other is called gauche.
• The staggered conformations are lower in energy than the eclipsed
conformations.
• The relative energies of the individual staggered conformations
depend on their steric strain.
• Steric strain is an increase in energy resulting when atoms are
forced too close to one another.
• Gauche conformations are generally higher in energy than anti
conformations because of steric strain.

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• An energy minimum and maximum occur every 60° as the
conformation changes from staggered to eclipsed. Conformations
that are neither staggered nor eclipsed are intermediate in energy.
• Butane and higher molecular weight alkanes have several C—C
bonds, all capable of rotation. It takes six 60° rotations to return to
the original conformation.
Energy
CH3CH3

H CH3 H H CH3
H H
H H CH3
H H H H
CH3 H

5.4 kcal mol-1

3.6 kcal mol-1

0.9 kcal mol-1 CH3 CH3

CH3 H CH3
CH3 H H
H H CH3 H
H H H H
H H H
H H CH3
CH3
H

Oo 60o 120o 180o 240o 300o 360o

Rotation
Fig 4.8 Energy changes that arise from rotation of the C-2-C-3 bon of butane
 Discussions
• The eclipsed conformations represent energy maxima in
the potential energy diagram ( Torsional strain and Van
der waals repulsion)
• While the barriers to rotation in a butane molecule are
larger than those of an ethane molecule
• The stability order of conformations are
CH3 CH3
H CH3 CH3CH3
H H CH3 H
H H
H H H H H H H H
CH3 CH3 H
H
anti ·´½»²æ gauche ²¿·Ö½»²æ part eclipsed ²¿·ÖÖصþ eclipsed È«Öصþ

Potential energy λÄÜ

Graph: Energy versus dihedral angle for butane

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The potential energy diagram of n-butane resembles that of
ethane in having three maxima and three minima, but differs in
that one of the minima is lower than the other two and one of
the maxima is of higher energy than the other two.

The minima correspond to staggered conformations.

Of these, the anti is lower in energy than the two gauche

conformations.

The energy difference between the anti and gauche

conformations in n-butane is about 0.6 kcal/mol.

The maxima correspond to eclipsed conformations, with the

highest-energy conformation being the one with the two methyl
groups eclipsed with each other.
The rotational profile of n-butane can be understood as a superimposition of
van der Waals repulsion on the ethane rotational energy profile.

The two gauche conformations are raised in energy relative to the anti by an
energy increment resulting from the van der Waals repulsion between the two
methyl groups of 0.6 kcal/mol.

The eclipsed conformations all incorporate 2.8 kcal/mol of torsional strain

relative to the staggered conformations, just as in ethane.

The methyl-methyl eclipsed conformation is further strained by the van der

Waals repulsion between the methyl groups.

The van der Waals repulsion between methyl and hydrogen is smaller in the
other eclipsed conformations.

The methyl/methyl eclipsed barrier is not known precisely, but the range in
experimental and theoretical values is between 4.0 and 6.6 kcal/mol, with the
most recent values being at the low end of the range
The conformation of other simple hydrocarbons can be interpreted
by extensions of the principles illustrated in the analysis of
rotational barriers in ethane and n-butane.

The staggered conformations correspond to torsional minima and

the eclipsed conformations to torsional maxima.

Of the staggered conformations, anti forms are more stable than

gauche.

Substitution of a methyl group for hydrogen on one of the carbon

atoms produces an increase of 0.4–0.6 kcal/mol in the height of
the rotational energy barrier.

The barrier in ethane is 2.88 kcal/mol. In propane, the barrier is

3.4 kcal/mol, corresponding to an increase of 0.5 kcal/mol for
methyl-hydrogen eclipsing.
When two methyl-hydrogen eclipsing interactions occur, as in 2-methylpropane,
the barrier is raised to 3.9 kcal/mol.

The increase in going to 2,2-dimethylpropane, in which the barrier is 4.7

kcal/mol, is 1.8 kcal/mol for the total of three methyl-hydrogen eclipsing
interactions.

For 2,2,3,3-tetramethylbutane, in which there are three methyl-methyl

interactions, the barrier is 8.4 kcal/mol. Rotational barriers in kcal/mol are
shown below.
 Rotational Barriers of Compounds
of Type CH3−X

• As with ethane, the barriers in methylamine and methanol

appear to be dominated by hyperconjugative stabilization of the
anti conformation.

• The barrier decreases (29 → 20 → 11) in proportion to the

number of anti H–H arrangements (3→2→1).
Conformations of Cycloalkanes
The Shapes of Cycloalkanes:
Planar or Nonplanar?
 Types of Strain
• Angle strain - results from distortion of bond
angles from normal values, for a tetrahedron 109.5o

• Torsional strain - eclipsing of bonds on

neighboring atoms

• Steric strain - strain that results from atoms being

too close together
• It turns out that cycloalkanes with more than three C
atoms in the ring are not flat molecules. They are
puckered to reduce strain.
Conformations of Cyclohexane
Cyclohexane

In reality, cyclohexane adopts a puckered “chair” conformation, which is more

stable than any possible other conformation.

The chair conformation is so stable because it eliminates angle strain (all C—C—C
angles are 109.5°), and torsional strain (all hydrogens on adjacent C atoms are
staggered).

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• In cyclohexane, three C atoms pucker up and three C atoms pucker down, alternating
around the ring.
• Each C in cyclohexane has two different kinds of hydrogens: (1) axial hydrogens are located
above and below the ring (along a perpendicular axis); (2) equatorial hydrogens are
located in the plane of the ring (around the equator).

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Each carbon atom in cyclohexane has one axial and one equatorial hydrogen
Six axial hydrogens perpendicular to the ring (parallel to the ring axis) and six equatorial hydrogens
near the plane of the ring

Each carbon is in the staggered conformation

The hydrogen atoms at opposite corners of the cyclohexane ring are
maximally separated in chair conformations -
Chair is the most stable conformation of cyclohexane
How to write the chair conformation?

•Note that the equatorial position has more room than

the axial position, so larger substituents are more stable
in the equatorial position.
Equatorial Conformation is Preferred
(link)
 Boat Conformation
Flagpole

HH H H H H
H
H
Unstable (the ecli

Stable (staggered conformation) Unstable (the eclipsed conformation)

 Boat conformation is less
stable than the chair

• All of the bond angles are close to tetrahedral but close

contact between flagpole hydrogens causes strain in boat.
• Eclipsed bonds give torsional strain to boat.
Boat Conformation

Less van der Waals strain and

Less torsional strain

Twisted boat is slightly more stable than boat

 Conformational Inversion/Mobility of cyclohexane

• An important conformational change in cyclohexane involves “ring-

flipping.” Rings can Flip from one Chair Conformation to Another Ring-flipping
is a two-step process.
• As a result of a ring flip, the up carbons become down carbons, and the
down carbons become up carbons.
Rapid process (activation energy = 45 kJ/mol)

48
Ring-flipping interconverts axial and equatorial
hydrogens in cyclohexane

49
 Flipping Chair Conformations
• All axial bonds become equatorial
• All equatorial bonds become axial
• All “up” bonds stay up
• All “down” bonds stay down
The inversion of chair conformation

a a
a e
e e

e
e
e
a
a a
a-bond e-bond
e-bond a-bond
axial up

eq. up
Axial-up becomes Equatorial-up
The inversion of conformations

Chair Half-chair

Boat Twist boat

The relative energies of the various conformations of
Cyclohexane (more than 99% of the molecules are chair conformation

Half Chair Half chair

10

Boat

10.8 kcal 10.8 kcal

5
Twist boat 7.1 kcal Twist boat
Chair Chair
5.5 kcal 5.5 kcal

Chair Half-chair Twist boat Boat Half-chair Chair

Twist boat
The Conformations of Cyclohexane
and Their Energies
Characterized by a small number of energy minima.
The most stable conformations are separated by barriers that are
somewhat higher and more easily measured than rotational barriers
in acyclic compounds or other ring systems.
The most stable conformation of cyclohexane is the chair.
The torsion angles are 55.90, compared with 60 for the “ideal” chair
conformation, and the axial C−H bonds are not perfectly parallel, but
are oriented outward by about 70.
The C−C bonds are 1.528Å, the C−H bonds are 1.119Å, and the
C−C−C angles are 111.050
Two nonchair conformations of cyclohexane that have normal bond
angles and bond lengths are the twist and the boat, both of which
are less stable than the chair.
Low-temperature IR spectroscopy - The chair was determined to be 5.5
kcal/mol lower in energy than the twist.

The twist and the boat conformations are more flexible than the chair,
but are destabilized by torsional strain, as the bonds along the “sides” of
the boat are eclipsed.

The boat conformation is further destabilized by a van der Waals

repulsion between the “flagpole” hydrogens.

Both this van der Waals repulsion and the torsional strain are somewhat
reduced in the twist Conformation.
 The first-order rate constant for ring inversion is 104–105 sec−1 at
270C. The enthalpy of activation is 10.8 kcal/mol.

 Calculation of the geometry of the transition state by molecular

mechanics suggests a half-chair form lying 12.0 kcal/mol above the
chair.
 The half-chair form incorporates 0.2 kcal/mol of strain from bond
length deformation, 2.0 kcal/mol of bond angle strain, 4.4 kcal/mol
of van der Waals strain, and 5.4 kcal/mol of torsional strain.

 The boat lies 1–2 kcal/mol above the twist-boat conformation and is
a transition state for interconversion of twist forms
• The chair forms of cyclohexane are 7 kcal/mol more stable than the boat
forms.
• The boat conformation is destabilized by torsional strain because the
hydrogens on the four carbon atoms in the plane are eclipsed.
• Additionally, there is steric strain because two hydrogens at either end of
the boat, the “flag pole” hydrogens, are forced close to each other.

Figure 4.14
Two views of the boat
conformation of cyclohexane

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