UNIT-2

ONFOR
CO RMATIIONAL
L ISOM
MERISM
M
In chemiistry, conforrmational isomerism is a form of sttereoisomeriism in whichh the isomerrs can
be intercconverted exclusively by b rotationss about form mally single bonds. Suuch isomerss are
generallyy referred too as conform mational isoomers or coonformers and a specificaally as rotamers
when thee rotation leaading to diffe ferent conforrmations is restricted
r (hindered) rotaation, in the sense
s
that theree exists a rotational enerrgy barrier thatt needs too be overcom
me to convert one confoormer
to anotheer. Conformational isom mers are thuss distinct froom the otherr classes of stereoisomer
s rs for
which innterconversio on necessarily involvess breaking and a reformiing of chem mical bonds. The
rotationaal barrier, or barrier to rootation, is thee activation energy
e requiired to intercconvert rotam
mers.

Conformmers of butan ne, shown inn Newman projection.

p The two gauuche as well as the anti form
are stagggered conform
mations

Types off conformattional isomeerism

Butane has
h three rotamers: tw wo gauche conformers,, which aree enantiomeeric and ann anti
conformeer, where thhe four carboon centres are
a coplanar. The three eclipsed connformations with
dihedral angles of 0°°,120° and 240°
2 are not considered to be rotameers, but are instead
i transsition
states.

mportant exam
Some im mples of connformationall isomerism include:
 1. Linear alkane conformations with staggered, eclipsed and gauche conformers, and
2. Ring conformation
o Cyclohexane conformations with chair and boat conformers.
o Carbohydrate conformation
3. Atropisomerism- due to restricted rotation about a bond, a molecule can become chiral
4. Folding of molecules, where some shapes are stable and functional, but others are not.

Conformations of Ethane  

While there are an infinite number of conformations about any sigma bond, in ethane two
particular conformers are noteworthy and have special names. In the eclipsed conformation, the
C-H bonds on the front and back carbons are aligned with each other with dihedral angles of 0
degrees. In the staggered conformation, the C-H bonds on the rear carbon lie between those on
the front carbon with dihedral angles of 60 degrees.

Energetically, not all conformations are equally favored. The eclipsed conformation of ethane is
less stable than the staggered conformation by 3 kcal/mol. The staggered conformation is the
most stable of all possible conformations of ethane, since the angles between C-H bonds on the
front and rear carbons are maximized at 60 degrees. In the eclipsed form, the electron densities
on the C-H bonds are closer together than they are in the staggered form. When two C-H bonds
are brought into a dihedral angle of zero degrees, their electron clouds experience repulsion,
which raises the energy of the molecule. The eclipsed conformation of ethane has three such C-H
eclipsing interactions, so we can infer that each eclipsed C-H "costs" roughly 1 kcal/mol.

Figure %: Eclipsing interactions in ethane. 

Steric Hindrance 

Eclipsing interactions are an example of a general phenomenon called steric hindrance, which
occurs whenever bulky portions of a molecule repel other molecules or other parts of the same
molecule. Because such hindrance causes resistance to rotation, it is also called torsional strain.
The 3 kcal/mol needed to overcome this resistance is the torsional energy. Note that this figure is
very small compared to the energy required to rotate around double bonds, which is 60 kcal/mol
(the bond energy of a C-C $\pi$ bond). At room temperature, ethane molecules have enough
energy to be in a constant state of rotation. Because of this rapid rotation, it is impossible to
isolate any particular conformation in the way that cis- and trans- alkenes can be individually
isolated. Although the term "conformational isomer" is sometimes used as a synonym for
conformations, conformations of a molecule are not considered true isomers because of their
rapid interconversion.

Figure %: Energy diagram for rotation about the C‐C bond in ethane. 

Conformations of n-butane 

The illustration of butane above is represented by the Newman Projections below by designating
the two middle carbons, one as the "front" and one as the "behind" carbon, and connecting the
two end methyl groups accordingly.
Conforrmations of
o cyclohexxane

A cyclohhexane confformation is i any of seeveral three--dimensionaal shapes thaat a cycloheexane

moleculee can assumee while mainntaining the integrity
i of its
i chemical bonds.

The inteernal angles of a flat regular

r hexaagon are 1220°, while the t preferredd angle bettween
successivve bonds in n a carbonn chain is abouta 109°,, the tetrahhedral anglee. Thereforee the
cyclohexxane ring tennds to assum me certain non-planar
n (
(warped) conformationss, which havve all
angles closer to 109°° and therefoore a lower strain
s energyy than the flaat hexagonall shape. The most
importannt shapes aree called chaair, half-chaair, boat, annd twist-boatt.[1] The molecule can easily
e
switch beetween these conformattions, and only two of them t — chaair and twisst-boat — caan be
isolated in
i pure form
m.

Chair coonformation
n

The two chair conformations haave the lowest total enerrgy, and are therefore thhe most stable. In
the basicc chair confo
ormation, thee carbons C1
C through C6 C alternate between twoo parallel pllanes,
one withh C1, C3 an nd C5, the other
o with C2,
C C4, and C6. The moolecule has a symmetryy axis
perpendicular to thesse two planees, and is coongruent to itself after a rotation off 120° aboutt that
axis. Thee two chair conformatio
c ons have the same shapee; one is conngruent to thhe other afteer 60°
rotation about that axis, or aftter being mirrored
m acrooss the meaan plane. Thhe perpendiicular
projection of the ring
g onto its meean plane is a regular heexagon. All C-C bonds are tilted rellative
to the meean plane, bu
ut opposite bonds
b (such as C1-C2 annd C4-C5) arre parallel too each other.

As a connsequence of o the ring warping,

w sixx of the 12 carbon-hyddrogen bondds end up allmost
perpendicular to thee mean planne and almoost parallel to the symm metry axis, with alternnating
directionns, and are said
s to be axial.
a H bonds lie almost paraallel to the mean
The otther six C-H m
plane, annd are said to
o be equatorrial.
The precise angles are such that the two C-H bonds in each carbon, one axial and one equatorial,
point in opposite senses relative to the symmetry axis. Thus, in a chair conformation, there are
three C-H bonds of each kind --- axial "up", axial "down", equatorial "up", and equatorial
"down"; and each carbon has one "up" and one "down", and one axial and one equatorial. The
hydrogens in successive carbons are thus staggered so that there is little torsional strain. This
geometry is often preserved when the hydrogen atoms are replaced by halogens or other simple
groups.

The conversion from one chair shape to the other is called ring flipping or chair-flipping.
Carbon-hydrogen bonds that are axial in one configuration become equatorial in the other, and
vice-versa; but their "up" or "down" character remains the same.

In cyclohexane, the two chair conformations have the same energy. At 25°C, 99.99% of all
molecules in a cyclohexane solution will be in a chair conformation.

In cyclohexane derivatives, the two chair conformations may have different energies, depending
upon the identity and location of the substituents. For example, in methylcyclohexane the lowest
energy conformation is a chair one where the methyl group is in equatorial position. This
configuration reduces interaction between the methyl group (on carbon number 1) and the
hydrogens at carbons 3 and 5; more importantly, it avoids two gauche butane interactions (of the
C1-CH3 bond with the C2-C3 and C5-C6 ring bonds). Similarly, cis-1,3-dimethylcyclohexane
usually has both methyls in the equatorial position so as to avoid interaction between them. In
six-membered heterocycles such as pyran, a substituent next to an heteroatom may prefer the
axial position due to the anomeric effect.

The preference of a substituent towards the equatorial conformation is measured in terms of its A
value, which is the Gibbs free energy difference between the two chair conformations, with the
substituent in equatorial or in axial position. A positive A value indicates preference towards the
equatorial position. The magnitude of the A values ranges from nearly zero for very small
substituents such as deuterium, to about 5 kcal/mol for very bulky substituents such as the tert-
butyl group.

Boat conformation

In the basic boat conformation (C2v symmetry), carbons C2, C3, C5 and C6 are coplanar, while
C1 and C4 are displaced away from that plane in the same direction. Bonds C2-C3 and C5-C6
are therefore parallel. In this form, the molecule has two perpendicular planes of symmetry as
well as a C2 axis. The boat conformations have higher energy than the chair conformations. The
interaction between the two flagpole hydrogens, in particular, generates steric strain. There is
also torsional strain involving the C2-C3 and C5-C6 bonds, which are eclipsed. Because of this
strain, the boat configuration is unstable (not a local minimum of the energy function).

Twist-boat conformation
The twist-boat conformation, sometimes called twist[1] (D2 symmetry) can be derived from the
boat conformation by applying a slight twist to the molecule about the axes connecting the two
unique carbons. The result is a structure that has three C2 axes and no plane of symmetry.

The concentration of the twist-boat conformation at room temperature is very low (less than
0.1%) but at 1073 Kelvin it can reach 30%. Rapid cooling from 1073 K to 40 K will freeze in a
large concentration of twist-boat conformation, which will then slowly convert to the chair
conformation upon heating

Half-chair conformation

The half-chair conformation is a transition state with C2 symmetry generally considered to be on

the pathway between chair and twist-boat. It involves rotating one of the dihedrals to zero such
that four adjacent atoms are coplanar and the other two atoms are out of plane (one above and
one below).

K.Anita priyadharshini,

Lecturer,

Dept.of Pharmaceutical Chemistry,

SRM College of Pharmacy