Conformational analysis

The different arrangements of the atoms in space that result from rotations of
groups about single bonds are called conformations of the molecule.
An analysis of the energy changes that a molecule undergoes as groups rotate
about single bonds is called conformational analysis.

Me
CO2H HO2C

CO2H

Me

H
Me

Me

Me
CO2H

CO2H

CO2H

Me

CO2H
Me

CO2H

Me

Me
OH
Me

HO

Et
Et

Different
conformations

Me

Me

HO

Et

OH

Different configurations

Et

Conformation of ethane
Eclipsed conformation

Staggered conformation
H

H
C

Wedge-and-dash
structures

60

Sawhorse
projections
H

H
H

H
HH

H
H

H
H

H
H

600

Newman
projections

600
H
H

The single parameter differentiating such conformers is an angle between two planes that
contain atoms ABC and BCD in themselves. This dihedral angle
is called a "torsion"
angle and is most frequently used for specification of the type of conformations.

 The energy level diagram shows that staggered conformation as a potential

energy minimum whilst the eclipsed conformation represents an energy
maximum (staggered conformation is lower in energy than the eclipsed by
2.9 kcal/mole (12 kJ/mole))

torsion

angles
also called
dihedral
angles

Torsion angles in degrees

Potential energy of ethane as function of torsion angles

Why is the eclipsed conformation higher in energy

than the staggered conformation?

The H-atoms are too small to get in each others

way-steric factors make up < 10% of the
rotational barrier in ethane

 Torsional strain
Caused by repulsion of the bonding electrons of one substituent with the bonding
electrons of a nearby substituent

filled orbitals repel

Stabilizing interaction between

filled C-H bond

The real picture is probably a mixture of all 3 effects

The rotational barrier is (12 kJ/mol) small enough to allow the conformational isomers
to interconvert million of times per second

Conformation of butane

Potential energy of butane as a function of torsion angle

A
B
C
D

"synclinal" or "gauche"
"anticlinal"
"anti-periplanar" or "anti"
"syn-periplanar" or "fully eclipsed"

"anti" conformation

''gauche'' conformation

"eclipsed"

or "synperiplanar" conformation

no torsional strain as the groups

are staggered and CH3 groups far
apart
van der Waals forces between two
CH3 groups are repulsive: the
electron clouds repel each other,
accounts for 0.9 Kcal/mole more
energy compared to "anti"
conformer
greatest energy due to torsional
strain and large van der waals
repulsive force between tne CH3
groups

Calculations reveal that at room temperature ~72% of the molecules of

butane are in the anti conformation, 28% are in gauche
conformation

Conformations and Conformers

Butane can exit in an infinite number of conformations (6 most important have
been considered), but has only 3 conformers (potential energy minima)-the two
gaucheconformations and the anti conformations
The preference for a staggered conformation causes carbon chains to
orient themselves in a zig zag fashion, see structure of decane

Cycloalkanes:
Ring strain

No of atoms in
ring

Internal angle in
planar ring

3
4
5
6
7
8

600
900
1080
1200
128.50
1350

* a measure of strain per C-atom

All internal angles 109.5 0C

109.50-internal
angle*

49.50
19.50
1.50
-10.50
-190
-25.50

109.50-internal angle
49.50
19.50
1.50
-10.50
-190
-25.50
Ring strain largest for 3-membered rings, then decreases
through a 4-membered ring and reaches a minimum for 5memberd ring.
Prediction: planar 5-membered ring should have the minimum
level of ring strain.
The ring strain keeps on increasing as the rings get larger after
the minimum at 5

 the difference between any two in series

is very nearly constant at around 660 kJ/mole
assuming there is no strain in the straight-chain
alkanes, each extra CH2 group contributes an
extra 658.7 kJ/mole to the heat of combution
if cycloalkane is strain free, its heat of combustion
should be n X 658.7 kJ/mole. If there is some strain
,more energy is given out on combustion

Look at the graph which shows, for each ring size:

(a) angle strain per CH2 group
(b) heat of combustion per CH2 group

 The greatest strain is in the 3-membered ring.

The strain decreases with ring size and reaches a minimum for 6-membered ring.
The strain then increases, but not as quickly as the angle calculation suggested: it
reaches a maximum at 9 and then decreases.
The strain remains constant at ~14, not increases steadily as the angle-strain suggested.

Why 6-membered ring is more strain free?

Why there is still some strain in 5-membered ring?

Cyclic compounds twist and bend to minimize the 3 different kinds of strain
1. Angle strain 2. Torsional strain
3. Steric strain

Cyclopropane

banana bonds
poor orbital overlap

Torsional strain

Good overlap
Strong bond

Poor overlap
Weak bond

Cyclobutane

to reduce torsional angle

Cyclopentane

The bent or envelope conformation of cyclopentane. In this structure

the front carbon atom is bent upwards. The additional bond angle strain in this
structure is more than compensated by the reduction in eclipsed
hydrogens. With little torsional strain and angle strain, cyclopentane
is as stable as cyclohexane. The molecule is flexible and shifts
conformation constantly.

HA

ring-flip

HA

HB
HB

Chair conformation
flagpole hydrogens
0

1.8 A

Sum of the van der

Waals radii = 2.4 A0

Boat conformation

HH

H
H

H
H

Newman projection of the

boat conformation

The easiest way to draw a twist-boat conformation

The energy difference between the chair, boat, and twist conformation of cyclohexane are low enough

to make their separation impossible at r.t. At room temperature approx. 1 million introversions occur
each other second.
More than 99% of the molecules are estimated to be in chair conformation at any given time

Monosubstituted cyclohexane
X

X
This conformation is lower in energy

Why?

For methylcyclohexane (X=CH3), the conformer with

the methyl group axial is 7.3 kJ/mol higher in energy
than the conformer with the methyl group equatorial.
Result: 20:1 ratio of equatorial:axial conformer at 200 C

1,3-diaxial interaction
H

H
X

H
H
H

H
H

H
H
H

The black bonds are antiperiplanar

(only one pair shown)

The black bonds are synclinal

(gauche)
(only one pair shown)

Conc. of equatorial conformer

K= Conc. of axial conformer

H
Me
Et
i-Pr
t-Bu
OMe
Ph

Equilibrium
constant

1
19
20
42
>3000
2.7
110

Energy diff. between

axial and equatorial
conformers
kJ/mol

0
7.3
7.5
9.3
>20
2.5
11.7

% with
substitutent
equatorial

50
95
95
98
>99.3
73
99

OH
OH

Preferred
conformation
t-butyl group
- a locking
group
OH

Preferred
conformation

OH

disfavoured

twist-boat conformation with both

t-Bu groups pseudoequatorial

Q. Write the prefered conformation for

Me

OH

i-Pr

Me
OH
favoured

Me
OH

CH3

CH3
CH3
CH3

CH3

CH3

1 gauche-butane interaction
0.9 kcal/mol

Difference in stability between

the conformational isomers

It should form a ()pair

CH3

CH3

4 gauche-butane interaction
4 x 0.9 kcal/mol = 3.6 kcal/mol

3.6 - 0.9 = 2.7 kcal/mol

CH3

CH3

CH3

CH3
CH3

H 3C

This has 3 gauche-butane

interactions
The two conformational isomers are mirror images

It exists as a dl-pair, but since barrier to rotation is low to allow separation.

Therefore the ()- pair is inseparable and hence the compound is optically inactive.

CH3
CH3
CH3

H3C

CH3

CH3

Very bad steric

situation ~ 5.5 kcal/mol (4 x 0.9 = 3.6 kcal/mol
+ Methyl-Methyl interaction)
CH3

CH3
CH3

H3C
CH3
CH3

It is a resolavable molecule
2-gauche-butane interaction = 1.8 kcal/mol

CH3
CH3

H3C
CH3

CH3
CH3

2-gauche-butane interaction, 2 x 0.9 = 1.8 kcal/mol

plane of symmetry : not resolavable

CH3

CH3
H3C
CH3

CH3

plane of symmetry

CH3

Why is the eclipsed conformation higher in energy than the staggered conformation?
As two nonpolar groups approach each other,
the van der Waals attractive force increases to
a maximum,then decreases and becomes
repulsive
The van der Waals radius one-half the
distance between two equivalent atoms at
the point of the energy minimum

van der Waals radii, A0

H

1.2

1.5

1.4

1.35

CH2
2.0
CH3
2.0

P
1.9

S
1.85

Cl
1.8
Br
1.95
I
2.15

The H-atoms are too small to

get in each others way-steric
factors make up < 10% of the
rotational barrier in ethane