____________________________________________________________________________________________________

Subject Chemistry

Paper No and Title 9; Organic Chemistry-III

Module No and Title 34 : Fluxional tautomerism

Module Tag CHE_P9_M34

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

TABLE OF CONTENTS

1. Learning Outcomes
2. Introduction
3. Degenerate Cope rearrangements
4. Fluxional tautomerism in inorganic compounds
5. Summary

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

1. Learning Outcomes
After studying this module, you shall be able to

• Know what are fluxional molecules

• Learn mechanism of fluxional tautomerism
• Identify examples of degenerate Cope rearrangements
• Evaluate fluxional tautomerism in bullvalene
• Analyze fluxional isomerism in organometallic compounds

2. Introduction
Cope rearrangement: It is a pericyclic reaction involving [3, 3] sigmatropic rearrangement of 1,
5-dienes. These rearrangements can be performed thermally or photo chemically. The Cope
rearrangement of dienes has found utility in a number of regioselective and stereo selective
syntheses of open ring systems.

2
1 3

1' 3'
2'
2
1 3

3'
1'
2'

2
CH2OH CH2OH
1 3

3'
1'
2'

Examples of Cope rearrangement

The sigmatropic rearrangements are an important class of pericyclic reactions which are classified
based on an order which is expressed by a set of two digits in brackets: [i, j], these numbers are
determined by counting the atoms over which each end of the σ bond has moved. Each of the
CHEMISTRY PAPER No. 9: Organic Chemistry-III
MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

original termini is given the number 1. Thus as can be seen Cope rearrangement represents a [3,
3] sigmatropic shift.

3. Degenerate Cope rearrangements

According to IUPAC the molecular rearrangement in which the main product is indistinguishable
from the main reactant is called a degenerate rearrangement. The term is used for both intra
molecular and intermolecular transfer of atoms or groups. The presence of degenerate
rearrangements is most appropriately visible by isotopic labelling or dynamic NMR techniques.

The degenerate rearrangement of 1, 5-hexatriene is the easiest illustration of Cope rearrangement

upon heating to 300 ºC. The Cope rearrangement may take place via one of two transition states,
involving a lower energy chair form transition state or a higher energy boat form transition state.
As the product is indistinguishable from the reactant, therefore we use isotopic labelling to ensure
that change has occurred.

Unlike Claisen rearrangement which also involve [3, 3] sigmatropic shift with conversion of vinyl
ethers into carbonyl double bonds, shifting the equilibrium completely to the product side, the
Cope rearrangement is reversible. Thus the position of equilibrium of Cope rearrangement is
determined by other factors such as substitution patterns, conjugation, ring strain and other
factors.

Degenerate Cope rearrangements are a type of valence isomerization reactions. Valence

isomerization are reversible in nature and generally rapid degenerate rearrangements that involve
the formation and rupture of single and/or double bonds, without migration of atoms or groups
takes place. Valence isomerization gives rise to fluxional molecules.

An elegant example for multiple degenerate Cope rearrangements is shown by bullvalene. Its
chemical formula is C10H10 . There is an unusual property associated with it that is the chemical
bonds making up the molecule are continuously rearranging. In bullvalene, the Cope
rearrangement may change the position of the cyclo propane ring from 3, 4, 5 to 1, 2, 8 position.
CHEMISTRY PAPER No. 9: Organic Chemistry-III
MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

But the molecule could also have undergone rearrangements to put this ring at 1, 7, 8 or 4, 5, 10
positions. Any of these could then undergo several different Cope rearrangements and yet do not
change the fundamental structure of bullvalene. The above mentioned reaction is known as
infinitely degenerate Cope rearrangement.

Degenerate Cope rearrangements in bullvalene

Molecules such as bullvalene are called fluxional molecules. Fluxional molecules might undergo
dynamics in such a way that some or all of their atoms interchange between symmetry-equivalent
positions. In Fluxional tautomerism compounds maintain the same number of component atoms
like in simple tautomerism. At equilibrium, these fluxional molecules exhibit several different
isomers and fluctuate rapidly among them. Bullvalene molecule contains a three-fold axis of
symmetry and three symmetrical and equivalent Cope systems are thus available to it. Each of

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

these 1, 5-diene units can undergo a Cope rearrangement again yielding bullvalene. In all, there
are more than 1.2

million tautomeric forms possible for bullvalene. At 140°C the reaction is so rapid that only one
peak is being observed for all H atoms in 1H-NMR. With three double bonds in the bullvalene
system, it should exhibit chemically non equivalent protons in NMR spectra, however due to its
“fluxional” structure it gives a sharp singlet in its proton NMR spectrum. This made it clear that
in order for the 10 protons, each bonded to a carbon atom, to be chemical-shift equivalent, “all ten
carbon atoms must inevitably wander over the surface of a sphere in ever changing relationship to
each other.

In general fluxional molecules are a unique class of molecules with no permanent structure.
Almost all molecules are fluxional in certain respects, for example: bond rotations in many of the
organic compounds. A molecule is considered to be fluxional if it shows line broadening in
spectroscopic signature due to chemical exchange (which is beyond Heisenberg’s uncertainity
principle). A few common features of fluxional molecules are;

Ø Fluxional molecules behave differently at different temperatures.

Ø While interchanging between different conformations many intermediates and meta-
stable forms are reached.
Ø Fluxionality provides diversity in structure of a molecule.

Several analogues of bullvalene such as semibullvalene and barbaralane also exhibit the
phenomenon of fluxional isomerism.

It was proposed that 3, 4- homotropilidine exists as rapidly inter converting chair-like and boat-
like conformational isomers and the Cope rearrangement takes place by way of the higher energy
boat-like isomer.

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

Unlike other cases where Cope rearrangement is favored by a chair conformation in the case of 3,
4 homo tropilidine, the rearrangements takes place via a boat conformation which are shown
below.

In the above conformations drawn for 3, 4 homotropylidine the interactions between H1 and H5
promote chair formation while positions of H2 and H3 are more similar to Cope transition state in
boat form. This is further illustrated below;

Chair to boat transition and Cope rearrangement for 3, 4-homotropylidine

CHEMISTRY PAPER No. 9: Organic Chemistry-III
MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

Overall for the reaction, the activation energy for the Cope rearrangement includes the difference
in energy between the two conformational isomers as well as the free energy of activation of the
Cope process. Another classic example of a fluxional molecule is dimethylformamide.

The two methyl groups in dimethyformamide are indistinguishable at higher temperature.

However, near room temperature, separate signals are seen for the non-equivalent methyl groups
in high resolution NMR. The rate of exchange has also been calculated for this process at the
temperature where the two signals are just merged.

Let us now look at some reactions of molecules exhibiting fluxional isomerism. Optically active
N, N’-dibenzylidene-1,2-diphenylene diamines (1) rapidly racemize at low temperature and loses
its optical activity due to fluxional isomerism in a cope rearrangement via a four centre chair
transition state. Heating at 120 °C in dimethyl sulphoxide gives a 1:1 mixture of dl and meso
forms.

Ladderane are an interesting class of compounds containing two or more fused cyclo butane
rings. The name arises from the resemblance of a series of fused cyclo butane rings to a ladder. A
useful mechanism for synthesis for ladderanes involves [2 + 2] photo cycloadditions, which is a
useful reaction for creating strained 4-membered rings. The molecule 1 shown below belongs to
ladderane polymer class.

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

Fluxional tautomerism in ladderaness

In a study it was shown that shiftamer 2 is fluxional at room temperature and undergoes
degenerate Cope rearrangement to give rise to 2’, which is equivalent to 2. Continued
indefinitely, the Cope rearrangement process leads to a pair of double bonds running down the
polymer chain running back and forth along the poly cyclo butane framework.

In another set of reactions, cyclooctatetraene (1) undergo dimerization to give 2 as the major
product. In a recent study the fluxional nature of dimer of cyclo octatetraene (2) with unsaturated
ketones in a Diels Alder reaction were examined.

Dimerization of cyclooctatetraene and further Diels Alder reaction with unsaturated ketones

The compound 2 can act as a reactive diene in Diels-Alder cycloadditions. It is also well-known
that 1 might as well undergo fast electrocyclic ring closure into its bicyclic valence tautomer 3,
but this electro cyclization is not thermodynamically favourable and thus only small amount of 3
is present at equilibrium. It was shown in the study that it takes a very small structural distortion
at the dihydro bullvalene end of the molecule to dramatically change the NMR spectrum of this
fluxional moiety (the dimer).

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

4. Fluxional tautomerism in inorganic compounds

Many organometallic compounds also exhibit fluxional tautomerism. For example, the iron
complex (dicarbonyl(η5-cyclopentadienyl)(cyclopenta-2,4-dien-1-yl)iron exhibits the
phenomenon of "ring whizzing". In the molecule, there are three types of chemically non
equivalent protons, however at 30 °C, the 1H NMR spectrum shows only two peaks, one typical
for the η5-C5H5 and the other assigned η1-C5H5. The singlet assigned to the η1-C5H5 ligand splits
at low temperatures owing to the slow hopping of the Fe center from carbon to carbon in the η1-
C5H5 ligand.

CO
CO
Fe
H
Ha
Ha

Hb
Hb
The structure of the ring whizzer [Fe(η -C5H5) (η1-C5H5)(CO)2].
5

Simple molecules such as NH3 and penta-coordinate molecules of trigonal pyramidal geometry
also exhibit a particular kind of low energy fluxional behavior called Berry pseudorotation.
Examples of such molecules are iron pentacarbonyl (Fe(CO)5) and phosphorus pentafluoride
(PF5). At higher temperatures, only one signal is observed for the ligands (e.g., by 13C or 19F
NMR) whereas at low temperatures, two signals in a 2:3 ratio can be resolved.

It has been reported that the Berry pseudorotation mechanism, is a type of vibration causing
molecules of certain geometries to isomerize by exchanging the two axial ligands for two of the
equatorial ones.

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism
____________________________________________________________________________________________________

5. Summary
Ø Cope rearrangement is a pericyclic sigmatropic [3, 3] shift.
Ø Molecular rearrangement in which the principal product is indistinguishable from the
principal reactant is called a degenerate rearrangement.
Ø Simple Cope rearrangements in 1,5-dienes are degenerate in nature.
Ø Bullvalene is a hydrocarbon with the chemical formula C10H10 with the unusual property
that the chemical bonds making up the molecule are constantly rearranging.
Ø Bullvalene may undergo 1209600 Cope rearrangements and still maintain the same
structure due to its fluxional nature.
Ø Fluxional molecules might undergo dynamics in such a way that some or all of their
atoms interchange between symmetry-equivalent positions.
Ø Fluxional molecules behave differently at different temperatures.
Ø Cyclooctatetraene undergoes dimerization to give an adduct which is a fluxional
molecule.

Ø Ladderane are an interesting class of compounds containing two or more fused cyclo
butane rings. They may exhibit phenomena of fluxional tautomerism.
Ø Many simple inorganic molecules such as PCl5 and Fe(CO)5 also exhibit the phenomenon
of fluxional isomerism.

CHEMISTRY PAPER No. 9: Organic Chemistry-III

MODULE No. 34: Fluxional tautomerism