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

http://www.brookscole.com/cgi-wadsworth/course_products_wp.pl?fid=M20bI&product_isbn_issn=0534389996&discipline_number=12http://www.brookscole.com/cgi-wadsworth/course_products_wp.pl?fid=M20bI&product_isbn_issn=0534389996&discipline_number=12

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