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Ref.

Mechanisms in Advanced Organic Chemistry

- R. P. Narain

Basic Principles of Organic Chemistry

- J. D. Roberts

March’s Advanced Organic Chemistry

- M.B. Smith & Jerry March

Fundamental of Organic Chemistry

- Graham Solomons

Conformational Analysis Conformational analysis: Pioneer, O.

Hassel (Norway) and D.H.R. Barton (Britain)

and both were awarded Nobel prize in 1969.

Conformation means the different

arrangement of atoms in space that result

from rotations of groups about a single

bond.

Conformational analysis: An analysis of

the eergy changes that occur as a molecule

undergoes rotations about single bonds

Two different 3D arrangements in space of the

atoms in a molecule are not interconvertible,

they are called configurations.

Configurations represent isomers that can be

separated.

If 3D arrangements in space of the atoms in a

molecule are interconvertible merely by C-C

free rotation, are called conformations.

Conformations represent conformers, which

are rapidly interconvertible and nonseparable.

Each possible structure is called a ‘conformer’

or ‘rotamer’.

The angle of torsion (dihedral

angle) angle between the X-C-

C and the C-C-Y planes

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Definitions

Gauche(staggered) - A low energy

conformation where the bonds on

adjacent atoms bisect each other

(60o dihedral angle), maximizing the

separation.

Eclipsed - A high energy

conformation where the bonds on

adjacent atoms are aligned with

each other (0o dihedral angle).

Definitions

Anti - Description given to two

substituents attached to adjacent

atoms when their bonds are at

180o with respect to each other.

Syn - Description given to two

substituents attached to adjacent

atoms when their bonds are at 0o

with respect to each other.

Syn

Types of strain

Torsional strain- The potential

energy arises due to the repulsion

between pairs of bonds caused by

the electrostatic repulsion of the

electrons in the bonds. Groups

are eclipsed.

Steric strain- The potential

energy arises due to the

repulsion between the electron

clouds of atoms or groups.

Groups try to occupy some

common space.

Rotational conformations of ethane

staggered, = 60

Sawhorse structures

Newman projections

eclipsed, = 0skew, = anything else

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rotate rear

carbon 60

60o Rotation causes torsional or eclipsing strain

Potential energy diagram of ethane

P.E

Dihedral angle

Ethane molecules have enough energy

to surmount this barrier, except at

extremely low temp. (−250 °C),

These conformers cannot be isolated except

at extremely low temperatures.

The barriers to rotation are far too small to allow

isolation of the different staggered conformations or

conformers, even at temperatures considerably below

room temperature.

The Newman projection of propane

rotate rear

carbon 60

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Propane conformations: larger barrier to rotationConformations of butane

Fig. I does not have torsional strain most stable.

Fig. III and V the two methyl groups are close enough to

each other the van der Waals forces between them are

repulsive the torsional strain is 3.8 kJ mol−1.

Fig. II, IV, and VI: energy maxima II, and IV have torsional

strain and van der Waals repulsions arising from the

eclipsed methyl group and hydrogen atoms; VI has the

greatest energy due to the large van der Waals repulsion

force arising from the eclipsed methyl groups.

Different conformations of butane

16.0 kJ/mol

6.0 kJ/mol

6.0

kJ/m

ol

4.0

kJ/m

ol

4.0

kJ/m

ol

4.0

kJ/m

ol

4.0

kJ/m

ol

11.0 kJ/mol

19.0 kJ/mol

The energy barriers are still too small to permit isolation of

the gauche and anti conformations at normal temperatures.

Energy changes that arise from rotation about the

C2–C3 bond of butane.

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Conformations of 2-methyl pentane

(I)

The conformers (I) and (II) are stable enough

for isolation at room temperature.

3,4-di(1-adamantyl)-2,2,5,5-tetramethylhexane

(I) (II)

All the conformations so far discussed have involved

rotation about sp3–sp3 bonds.

The actual dihedral angles are distorted from the 60 angles shown in the

drawings, owing to steric hindrance between the large groups.

Conformations of ethylene glycol

I II III IV

Order of stability (because of intramolecular hydrogen bonding)

Gauche conformation (III) > anti conformation (I) >

partially eclipsed (II) > fully eclipsed conformation (IV)

Similar conformational stability (gauche

conformation is most stable) is observed in case

halohydrins.

Rotational Barriers

3.4 kcal/mol

14.23 kJ/mol

3.9 kcal/mol

16.32 kJ/mol

4.7 kcal/mol

19.66 kJ/mol

CH3CH(CH3)2 CH3CH(CH3)3CH3CH2CH3

CH3CH3

12 kJ/mol

1kcal/mole=4.184 kJ/mole

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Rotational Barriers

The C–C bond is more than 40% longer than

the C–H bond, reducing the overall steric

crowding.

C–H bond length is shorter than C–Y bonds

(relative distance r2 is greater than r1)

3.3 kcal/mol

13.81 kJ/mol

3.8 kcal/mol

15.90 kJ/mol

3.2 kcal/mol

13.39 kJ/mol

CH3CH2ClCH3CH2F CH3CH2Br CH3CH2I

3.7 kcal/mol

15.48 kJ/mol

F atom is about 2 times larger then H, Cl is three times

as large, and Br and I being roughly 3.5 and 4 times the

size of H.

Rotational barrier of haloalkanes

4.8 kcal/mol 6.1 kcal/mol 10.8 kcal/mol

CH3CHCl2 CH2ClCH2Cl CCl3CCl3

10 kcal/mol

CH3CHCl3

Rotational barrier of haloalkanes

Hexachloroethane has a barrier only about

20% higher than 1,2-dichloroethane.

0.03 Å increase in the C–C bond length (about

2%) hexachloroethane, caused by the

extensive dipole repulsion.

Energy diagram of 1,2-dichloroethane

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Conformation of 1,2-difluoroethane

1,2-difluoroethane suffers dipole repulsion as the fluorine atoms approach

each other, the gauche form is more stable than the anti conformer (ΔHº

= 0.6 kcal/mol).

In 1,2-dihaloethanes, anti conformations are more stable in the chloro, bromo

and iodo compounds, while gauche conformation stable in the difluoride

98 % 1 % 1 %

Meso-2,3-dichlorobutane

62 % 37 % 1 %

2S,3S)2,3-dichlorobutane

Conformation equilibria

Acyclic systems with unsaturated

substituents: σ-π Conjugation

Rotation about the bond is easier than propane.

Two reasons:

1. One group fewer on the sp2 carbón

2. One of the bond angles is wider.

Propene (Y=Me, X=CH2)

Stabilization arises from -∗ interactions. The major

effect is a transfer of electron density from the methyl

C−H bonds to the empty ∗ orbital.

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Rotamers of propene

Rotation of methyl, a C–H bond eclipses either an

sp2C–H bond or C=CH2 bond, but not simultaneously.

Conformer eclipsed with C=CH2 bond has lower energy,

possibly a stabilizing interaction between σ-C–H bonds

of methyl and the π* antibonding orbital.

Energy diagram of propene

The energy of this rotation follows a simple sine-curve.

Smaller amplitude (ca. 2 kcal/mol) smaller than ethane.

Rotamers of 1-butene

The overall rotational barrier is reduced compared to propene

Compared to propene, in 1-butene doubles the number of

eclipsed and bisected conformers.

The eclipsing shown by magenta colored arrows in B2 is

referred to as allylic 1,2-strain

Energy diagram of 1-butene

CH3-CH2-CH=CH2

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Rotamers of (E)-2-Pentene

The E-isomer, has a rotational profile very

similar to that of 1-butane.

Since the C-1 methyl is directed away from theethyl group, this is not surprising.

Rotamers of (Z)-2-Pentene

In (Z)-2-pentene, C-1 methyl is cis to the ethyl group,

leading to severe steric crowding in E1 and B1.

The perpendicular conformation, P, is lower in energy

than either E2 or B2.

Energy diagram of (Z)-2-Pentene Rotamers of acetaldehyde

Conformation of acetaldehyde is similar to propene.

The energy for rotation is half that of propene,

reflecting the absence of a hydrogen on the oxygen

atom.

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Energy diagram of acetaldehyde Rotamers of propanal

Conformational energy profile of propanal differs

significantly from that of 1-butene.

Conformer E1 is more stable than E2 by roughly 0.8

kcal/mol, reflecting the relatively small size of oxygen.

Energy diagram of propanal

1-butene

Compared to 1-buten relatively small size of oxygen

stabilize E1 more than E2 in propanal.

When the alkyl substituent becomes too sterically

hindered, the hydrogen-eclipsed conformation becomes

more stable.

More stable in which the alkyl group is to be anti

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Cyclohexane

Axial and equatorial bond

6 axial perpendicular to ring

6 equatorial in ‘plane’ of ring

Each C has axial and equatorial

Each face has 3 axial and 3 equatorial

Ring flip chain conformation interconvert at RT

Exchange axial and equatorial position

Conformation of cyclohexane

This chair

conformer has

four 1,3-diaxial

interactions

Cis-1,2-dimethylcyclohexane

Two equivalent conformations:

Each has one axial methyl group and one equatorial methyl group

First conformation:

o 1 gauche interaction =3.8 kJ/molo 2 CH3-H 1,3-diaxial interaction (2 3.8) =7.6 kJ/mol

=11.4 kJ/mol

Second conformation (ring flip):

o 1 gauche interaction =3.8 kJ/molo 2 CH3-H 1,3-diaxial interaction (2 3.8) =7.6 kJ/mol

=11.4 kJ/mol

Trans-1,2-dimethylcyclohexane

Two conformations are not equivalent:

Most stable conformation has both methyl groups equatorial.

First conformation:

o 4 CH3-H 1,3-diaxial interaction (4 3.8) =15.2 kJ/molo No gauche interaction = 0.0 kJ/mol

=15.2 kJ/mol

Second conformation (ring flip):

o 1 gauche interaction =3.8 kJ/molo No 1,3-diaxial interaction =0.0 kJ/mol

=3.8 kJ/mol

Almost exclusively exist in diequatorial conformation

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Cis-1,3-dimethylcyclohexane

Two conformations are not equivalent;

most stable conformation has both methyl groups equatorial.

First conformation:

o No gauche interaction = 0.0 kJ/molo 4 CH3-H 1,3-diaxial interaction (4 3.8) =15.2 kJ/mol

=15.2 kJ/mol

Second conformation (ring flip):

o No gauche interaction =0.0 kJ/molo No CH3-H 1,3-diaxial interaction =0.0 kJ/mol

= 0.0 kJ/mol

Trans-1,3-dimethylcyclohexane

Two conformations are not equivalent;

most stable conformation has both methyl groups equatorial.

First conformation:

o No gauche interaction = 0.0 kJ/molo 2 CH3-H 1,3-diaxial interaction (2 3.8) =7.6 kJ/mol

=7.6 kJ/mol

Second conformation (ring flip):

o No gauche interaction =0.0 kJ/molo 2 CH3-H 1,3-diaxial interaction (2 3.8) =7.6 kJ/mol

= 7.6 kJ/mol

Cis-1,4-dimethylcyclohexane

Two equivalent conformations:

Each has one axial methyl group and one equatorial methyl group

First conformation:

o No gauche interaction =0.0 kJ/molo 2 CH3-H 1,3-diaxial interaction (2 3.8) =7.6 kJ/mol

=7.6 kJ/mol

Second conformation (ring flip):

o No gauche interaction =0.0 kJ/molo 2 CH3-H 1,3-diaxial interaction (2 3.8) =7.6 kJ/mol

=7.6 kJ/mol

Trans-1,4-dimethylcyclohexane

Two conformations are not equivalent;

most stable conformation has both methyl groups equatorial.

First conformation:

o No gauche interaction = 0.0 kJ/molo 4 CH3-H 1,3-diaxial interaction (4 3.8) =15.2 kJ/mol

=15.2 kJ/mol

Second conformation (ring flip):

o No gauche interaction =0.0 kJ/molo No 1,3-diaxial interaction =0.0 kJ/mol

=0.0 kJ/mol

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Isomer Conformation Interaction,kJ/mol

Cis-1,2 11.4 and 11.4

Trans-1,2 3.4 and 15.2

Cis-1,3 0.0 and 15.2

Trans-1,3 7.6 and 7.6

Cis-1,4 7.6 and 7.6

Trans-1,4 0.0 and 15.2

Conformations and energies of dimethyl

cyclohexanes

Compound Orientation -DH°

cis-1,2-dimethyl ax-eq 5223

trans-1,2-dimethyl eq-eq 5217*

cis-1,3-dimethyl eq-eq 5212*

trans-1,3-dimethyl ax-eq 5219

cis-1,4-dimethyl ax-eq 5219

trans-1,4-dimethyl eq-eq 5212*

*more stable stereoisomer of pair

Heats of combustion of

isomeric dimethylcyclohexanes

Conformations of cyclohexanone

Carbonyl carbon atom in cyclohexanone makes

it less stable compared to parent compound,

cyclohexane.

Equatorial hydrogen atoms on -carbon are

nearly eclipsed with carbonyl oxygen,

destabilized by steric repulsion.

2-Alkyl cyclohexanone

An equatorial alkyl group at C-2 of a

cyclohexanone is more stable then that of axial.

Conformation with axial alkyl group at C-2 has 3,5-

diaxial interaction with syn-diaxial hydrogens.

The conformational energies for 2-methyl group in

cyclohexanone is similar to cyclohexane, but

somewhat smaller for ethyl and isopropyl.

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3-Alkyl cyclohexanone

Alkyl group at C-3 of cyclohexanone is more

stable then that of a alkyl group in cyclohexane.

Because of reduced 1,3-diaxial interactions.

Haloketone effects in cyclohexane

Substituents at C-2 can assume an axial or

equatorial position depending on steric and

electronic influences.

In 2-bromocyclohexanone the axial

conformation is more stable than the

equatorial by 2-3 kcal/mol

a-Bre-Br

Less stable More stable

Haloketone effects in cyclohexane

In 2-bromo-4,4-dimethylcyclohexane the

equatorial bromine atom makes it more stable.

The axial methyl group does not allow the

bromine atom to adopt an axial position

Less stableMore stable

Haloketone effects in cyclohexane

Boat shaped conformation of cis 2,4-di-t-butyl-

cyclohexanone is more stable than chair

conformation

Chair ChairBoat

More stable

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Haloketone effects in cyclohexane

Substituents at C-2 is an axial or equatorial depending

on steric and electronic influences.

F 173

Cl 454

Br 714

I 885

X % Axial Conformation

Methods used to determine conformations:

X-ray and electron diffraction

IR, Raman, UV, NMR

microwave spectra, photoelectron spectroscopy

Optical Rotatory Dispersion and CD

measurements.