Conformational Analysis

Carey & Sundberg: Part A; Chapter 3

 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.

Different Different
conformations configurations
Conformations of ethane
 Torsion or Dihedral angle

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.
 Potential energy of ethane as function of torsion angles

staggered conformation has potential energy minimum

eclipsed conformation has potential energy maximum
staggered conformation is lower in energy than the eclipsed by
2.9 kcal/mole (12 kJ/mole)
 Conformations of butane

D
B

Potential energy of butane as a function of torsion angle

A synclinal or gauche
B anticlinal
C anti-periplanar or anti
D syn-periplanar or fully eclipsed
 C anti-periplanar or anti
No torsional strain as the groups are staggered and CH 3 groups
are par apart

A synclinal or gauche
van der Waals forces between two CH3 groups are repulsive: the
electron clouds repel each other which accounts for 0.9
Kcal/mole more energy compared to anti conformer

B anticlinal
Calculations reveal that at room temperature ~72% of the molecules of
butane torsional
are in thestrain andconformation,
anti large van der waals repulsive
28% are forces
in gauche
between the H and CH3 groups
conformation

D syn-periplanar or fully eclipsed

Highest energy due to torsional strain and large van der

waals repulsive force between the CH 3 groups
 Butane in Chair Form
H H
H CH3
H H H H
H H
H H
CH3 H
H H
staggered gauche
conformation conformation

H H
H
1,3-diaxial
CH3 CH3 H
CH3
H H CH3
H H
H H
H H
H H
H
H H
H
gauche A 1,3-diaxial interaction is the same as a gauche
conformation conformation!!

H H H
H H H

H H H H
H H H
H
CH3 CH3 CH3 CH3
H H H
An equatorial substituent is more stable because it is in the staggered conformation.
staggered
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
The Syn-Pentane Conformation
CH3 CH3

CH3 CH3

CH3
CH3
G = 5.5 kcal/mol
H3C

H3C
2 gauche and 1 syn-pentane fully staggered

syn-pentane = G 2 gauche = 5.5 2(0.88) = + 3.7 kca/ mol

CH3 H CH3 H CH3 H

CH3 CH3 CH3

gauche gauche syn-pentane

Conformation and hydrogen bonding
 Conformation of butane-2,3-diols

Intramolecular H-bond is always stronger in the active forms,

they are more stable than the meso isomers
Conformation of 2,3 dibromobutane

Meso is more stable than active form

 Cyclohexane

Chair conformation

Sum of the van der Waals radii = 2.4 A0

Boat conformation

Newman projection of the

boat conformation
Ring flipping or
inversion
 Interconversions of Cyclohexane

Chair Half boat Twist boat boat

Erel=0.0 kcal/mol Erel=10 Erel=5.5 Erel=6.5

Twist boat Half boat Opposite sense Chair

Opposite sense

Planar Erel= very large >20 kcal/mol

 Monosubstituted cyclohexane

This conformation is lower in energy

Why?
When X=CH3, conformer with Me in axial is higher in
energy by 7.3 kJ/mol than the corresponding equatorial
conformer.
Result: 20:1 ratio of equatorial:axial conformer at 200 C
1,3-diaxial interaction

The black bonds are anti-

periplanar
(only one pair shown)

The black bonds are synclinal

(gauche)
(only one pair shown)
X Equilibrium Energy diff. between % with
constant axial and equatorial substitutent
conformers equatorial
kJ/mol
H 1 0 50
Me 19 7.3 95
Et 20 7.5 95
i-Pr 42 9.3 98
tBu >3000 >20 >99
OMe 2.7 2.5 73
Ph 110 11.7 99
 Diastereomeric, chiral and therefore resolvable

Enontiomeric, chiral and not resolvable

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.
 Diastereomers, achiral

Identical, chiral

cis-isomer is more stable than trans isomer

 Identical, achiral

Diastereomers, achiral

Both have plane of symmetry, achiral

Trans is stable than cis

1-tert-Butyl-3-Methylcyclohexane
Conformational equilibrium in 1-phenyl-1-methyl cyclohaxane
 Preferred Conformations

Disfavoured

t-butyl group
a locking group

Twist boat
 oxidation

Relief of the steric strain in the transition state

 Saponification

less hindered ester will react faster

Write preferred conformation for
Rigid molecules from cyclohexane conformers
 Cyclopentane

Envelope Half chair

The energy difference is little

one carbon atom is bent upwards
The molecule is flexible and shifts conformation constantly
Hence each of the carbons assume the pivotal position in rapid
succession .
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.
 Cyclopentane

H
H
H H
H H H H
H H
H H H
H H
H
H H H H
Envelope Half-Chair

Twolowestenergyconformationsofcyclopentane(10envelopeand10halfchairconformations)
differbyonly0.5kcal/mol.Theyareinrapidconformationalflux(pseudorotation)whichcausesthe
moleculetoappeartohaveasingleoutofplaneatom"bulge"whichrotatesaboutthering.

Sincethereisno"natural"conformationofcyclopentane,theringconformstominimize
interactionsofanysubstituentspresent.
H
H
H H
H H H
H O
H
H
H H H
H H H
H

A single substituent strongly prefers the A carbonyl or methylene prefers the planar
equatorial position of the flap of the envelope position of the half-chair (barrier 1.15
(barrier ca. 3.4 kcal/mol, R = CH3). kcal/mol for cyclopentanone).

Me

Me
H H
1,2 Disubstitution prefers
trans for steric/torsional
reasons (alkyl groups) and 1,3 Disubstitution: Cis-1,3-dimethyl cyclopentane
dipole reasons (polar groups). only 0.5 kcal/mol more stable than trans.
 Cyclobutane
ax ax Eclipsing torsional strain overrides
eq increased bond angle strain by puckering.
eq eq
eq
ax Ring barrier to inversion is 1.45 kcal/mol.
ax

n G = 1 kcal/mol favoring R = Me equatorial

n 1,3 Disubstitution prefers cis diequatorial to trans

by only 0.58 kcal/mol for di-bromo compound.

n 1,2 Disubstitution prefers trans diequatorial to cis

by 1.3 kcal/mol for diacid (roughly equivalent to the
cyclohexyl analogue.)
 Cyclobutane

to reduce torsional angle

Cyclobutane
Interplanar angle 35
 Bicyclic Systems

H
3
Gauche-butane interactions
H C1 C2
4 2 C1 C3
C4 C3
1
G(est) = 3(0.88) = 2.64 kcal/mol

Can you estimate the energy difference between the two methyl-decalins shown below?

Me Me

H H
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