Conformational Analysis
Based on
Claydens Organic Chemistry, Chapter 16
The aims of this chapter are to ..
How single bonds are free to rotate, but spend most of their
time in just two or three well-defined arrangements
Why rings of atoms are usually not planar, but puckered
How to use the known arrangements of the atoms in a six-
membered ring to predict and explain their reactions
Bond rotation allows chains of atoms to adopt a number
of conformations
we can rotate about as many single bonds
as we like but we cant break any bonds.
Rotation is possible
about single bonds
and this rotation
means that, while the
localized arrangement
of atoms stays the
same, the molecule
as a whole can adopt
a number of different
shapes
Conformation and configuration
structures that can be interconverted by rotating about single bonds - different
conformations of the same molecule.
structures can only be interconverted by breaking a bond - different configurations
Configurations can be interconverted only by breaking bonds. Compounds with
different configurations are called stereoisomers
Conformations of ethane
Ethane has two extreme conformations called the staggered
Newman projection:
Ethane has two extreme conformations called the staggered and eclipsed
conformations
Why is the eclipsed conformation higher in energy than the staggered onformation?
- the electrons in the bonds repel each other
and this repulsion is at a maximum in the
eclipsed conformation.
- there may be some stabilizing interaction
between the CH s bonding orbital on one
carbon and the CH s*antibonding orbital on
the other carbon, which is greatest when the
two orbitals are exactly parallel: this only
happens in the staggered conformation.
Conformations of butane
The staggered conformations will be energy minima when the two methyl groups
are furthest from each other in the trans conformation
The different stable conformations of butane are some sort of isomers. They are
called conformational isomers or conformers for short.
The staggered conformations will be energy minima when the two methyl groups
are furthest from each other in the trans conformation so this will be a slightly lower
minimum than the two gauche conformations.
Ring Strain
Six-Membered Ring
All the carbon atoms are not in the same plane, and there is no strain because
all the bond angles are 109.5.
boat conformationboat conformation - In this conformation there
are still four carbon atoms in one plane, and the
other two are both above this plane. The four
carbon in the plane are different from the ones
above. However, this is not a stable conformation
of cyclohexane, even though there is no bond
angle strain
Smaller Rings
Rings larger than 3 atoms
are not flat
Larger rings have many more
possible conformations than
smaller rings and are more
difficult to analyze
Cyclic molecules can
assume nonplanar
conformations to reduce
the eclipsing interactions
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A Closer Look at Cyclohexane
no eclipsing CH bonds, all the bonds are fully staggered, giving the lowest
energy possible. This is why the chair conformation is strain-free.
all the CH bonds
are eclipsed, and
there is a bad
interaction
between the
flagstaff CH
bonds
Conformational Analysis (part 2)
Based on
Claydens Organic Chemistry, Chapter 16
Cyclohexane
There are two types of protons - one type stick either vertically up or down and
are called axial hydrogen;
There are two types of protons - one type stick either vertically up or down and
are called axial hydrogen; the other sort stick out sideways are called equatorial
hydrogen.
Substituted Cyclohexane
In a monosubstituted cyclohexane, there can exist two different chair conformers:
- one with the substituent axial, the other with it equatorial;
- the two chair conformers will be in rapid equilibrium but they will not have the
same energy;
- the conformer with the axial substituent is higher in energy, which means
there will be less of this form present at equilibrium
Reasons why axial conformer is higher in energy than the equatorial conformer:
- in the equatorial conformer the CX bond is anti to two CC bonds,
Reasons why axial conformer is higher in energy than the equatorial conformer:
- axial conformer is destabilized by the repulsion between the axial group X and
the two axial hydrogen atoms on the same side of the ring (1,3-diaxial
Interaction).
- in the equatorial conformer the CX bond is anti to two CC bonds, while, for
the axial conformer, the CX bond is gauche to two CC bonds
What happens with more than one substituent on the ring?
When there are two or more substituents on the ring, stereoisomerism is possible.
Consider 1,4-cyclohexanediol,
- there are two isomers - cis isomer where both the substituents are either above
- trans isomer where one hydroxyl group is above the ring whilst the second is
below
or below the cyclohexane ring;
both substituents
axial or both
equatorial
one substituent
is axial and the
other is
equatorial
Locking Groups
t-butyl group always prefers an equatorial position in a ring
In cis-1,4-di-t-butylcyclohexane, the compound puckers into a twist boat so that the
two large groups can both be in equatorial positions (or pseudoequatorial, since
this is not a chair
Decalins
Two diastereoisomers are possible,
depending on whether the H atoms at
the ring junction are cis or trans
When a cyclohexane ring inverts, the
substituents that were equatorial
become axial and vice versa
Axially and Equatorially Substituted Rings React Differently
Recall:
If the
conformation
of the
molecule is
fixed and if the
reaction is
SN2: if the
leaving group
is axial, then
the incoming
nucleophile
will end up
equatorial and
vice versa
What do you think would
happen if a cyclohexane
derivative underwent an
SN2 reaction?
Substitution reactions are not very common for substituted cyclohexane because
the substituted carbon in a cyclohexane ring is a secondary.
To encourage an
SN2 mechanism, a
good attacking
nucleophile and a
good leaving group
is required.
Substitution of an axial
substituent proceeds faster
than the substitution of an
equatorial substituent. This
is due to the direction of
approach of the nucleophile
line of attack is hindered by the (green) axial
Epoxides
ring flip
Recall: epoxides can be
formed from compounds
containing an adjacent
OH group and a leaving
group by treatment with
base
Epoxide ring-opening reaction
with a nucleophile is essentially
the reverse of the epoxide
formation reaction
ring opening of cyclohexene oxides always
leads directly to diaxial products
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