ELECTROCYCLIC PROCESS IN

HETEROCYCLIC RING
SYNTHESIS

Presented by:
SHAIK RIYAZ
HT No. 20004P-1027
M. Pharmacy I Semester
Dept. Of Pharmaceutical Chemistry
University College Of Pharmaceutical Sciences
Kakatiya University, Warangal
 Electrocyclic process in Heterocyclic
ring synthesis
Definition: an electrocyclic reaction is a type of pericyclic rearrangement
where the net result is one pi bond being converted into one sigma bond or
vice versa.
• Depending on the type of reaction (photochemical or thermal) and the
number of pi electrons, the reaction can happen through either a conrotatory
or disrotatory mechanism.
• The type of rotation determines whether the cis or trans isomer of the product
will be formed
• Reactions can be either ring-opening or ring-closing
• Ring synthesis is a ring forming reaction or ring-closing reaction that
introduce one or more rings into a molecule.
• A heterocycle forming reaction is such a reaction that introduces a new
heterocycle.
Examples: ring opening reaction of 3,4- dimethylcyclobutene

The cis isomeneer exclusively yields cis,trans-hexa-2,4-diene whereas the trans isomer gives
the trans,trans diene.
In Heterocyclic compounds:
Ring-opening of Benzocyclobutene.

Ring-closure reaction of Benzocyclobutene.

• An atom or group of atoms sifts from one position to another. The
process involves breaking of a bond and forming of a new bond.
 Methods of analysing Elecrocyclic reactions
1. The frontier molecular orbital (FMO)
2. Orbital symmetry correlation diagrams
3. Huckel-Mobius theory or Perturbation Molecular Orbital (PMO)

1. Frontier Molecular Orbital (FMO) approach:

The mechanism of electrocyclic reactions can be understood in
terms of frontier molecular orbital (FMO) theory and the outcome
of reactions can be predicted using the Woodward- Hoffman rules.
The pathway of such reactions is determined by the symmetry
properties of the orbitals that are directly involved. The orbital
symmetry must be same during overall mechanism.
⚫ In electrocyclic reactions, only one reactant is involved and thus only
the highest occupied molecular orbital (HOMO) needs to be
considered. Thus, the stereochemistry of the reactions is controlled by
the symmetry properties of the HOMO of the reacting system. These
reactions take place thermally or photochemically.
⚫ In thermal condition, the ground state HOMO is involved in the
reaction, but in photochemical condition, the excited state HOMO
involved.
⚫ The orbitals of terminal atoms of HOMO rotate through 900 to allow
of their potential overlap.
⚫ The rotation occurs in the same direction, i.e., clockwise or
counterclockwise is called conrotatory process.
⚫ But rotation occurs in the opposite direction is called disrotatory
process. The rotation of terminal orbital depends on the type of
polyene, i.e., number of double bond and condition of reaction. It is
illustrated by following system.
In thermal condition ground state HOMO has terminal orbital with opposite phase,
conrotatory motion lead to a bonding interaction and thus to the formation of cyclobutene
while disrotatory movement results in an antibonding situation. In thermal electrocyclic
reaction of a 4n π-system, therefore, only conrotatory motion is allowed
In the case of photochemical condition, irradiation of diene will result in the promotion of an
electron into the orbital next higher energy level and ground state LUMO becomes the excited
state HOMO which has terminal orbital with the same phase. There is conrotatory motion
leading to an antibonding situation, while disrotatory motion results in a bonding interaction
and the formation of cyclobutane.
Electrocyclic reactions are completely stereo specific:
For example ring closure of (2E,4Z,6E)-2,4,6- octatriene yields a single product
with cis methyl groups on the ring.

Moreover, the stereochemistry of the product of an electrocyclic reaction also

depends on reaction condition,
i.e., Thermal or photochemical reaction conditions.
⚫ For example Cyclization of (2E,4E)-2,4-hexadiene
with heat forms a cyclobutane with trans methyl groups, whereas
cyclization with light forms a cyclobutane with cis methyl groups.
2. Orbital symmetry correlation diagrams.

•The analysis of electrocyclic reactions can also be done by orbital correlation

diagrams.
•This approach focuses attention on the orbital symmetries of both reactants and
products and considers the symmetry properties of all the orbitals.
•In any concerted process, the orbitals of the starting material must be smoothly
transformed into orbitals of product through a transition state having the same
symmetry.
•Thus, the symmetry must be conserved throughout the reaction. The orbital
symmetry rules can be generalized from conjugated polyenes to any type of the
conjugated system,
•In case of the conrotatory process, the element of symmetry.
• That maintained throughout the reaction is the twofold rotation axis.
However, in disrotatory motion, the plane of symmetry is
maintained throughout the reaction.

In case of 4n π-system e.g. the cyclobutene-butadiene interconversion, the four π-

orbitals of butadiene are converted into the two π- and two σ-orbitals of the ground
state of cyclobutene.

The π-orbitals of butadiene are designated as ψ1,ψ 2, ψ3, and ψ4 and for
cyclobutene, the four orbitals are π, σ, π *, and σ*. If the reaction takes place
through conrotatory motion, then C2 axis of symmetry is maintained throughout
the reaction.

The molecular orbitals must be either symmetric (S) or antisymmetric (A). Same
symmetry orbitals must correlate to each other.
Hint to correlation diagrams:
If the reaction takes place through conrotatory motion
If the reaction takes place through Disrotatory motion
In 4n π-system, therefore, conrotatory motion occurs under
thermal condition.

In 4n π-system, therefore, disrotatory motion occurs under

photochemical condition.
 Inter conversion of 1,3,5-hexatriene and
cyclohexadiene 4n+2 π-system
•thecorrelation diagrams can be constructed
in
analogous manner for the conrotatory and disrotatory
modes for 4n+2 π-system
•e.g. interconversion Of 1,3,5-hexatriene and
cyclohexadiene.
•In Ring opening reaction, the four π- and two σ- orbitals of the
ground state of cyclohexadiene are converted into the six π-
orbitals of 1,3,5-hexatriene. The π-orbitals of 1,3,5-hexatriene
are ψ1, ψ2, ψ3, ψ4, ψ5 and ψ6 and for cyclohexadiene, the six
orbitals are π1, π2 π3, π4, σ, and σ*.
If the reaction takes place through conrotatory motion
If the reaction takes place through Disrotatory motion
In 4n+2 π-system, therefore, Disrotatory motion occurs under
thermal condition

In 4n+2 π-system, therefore, conrotatory motion occurs

under photochemical condition.
Example of electrocyclic reaction 4n systems:
 Sigmatropic rearrangements
A concerted reaction of the
type.

In which a group migrates with its σ-bond within a π- framework an one or

a polyene is called a sigmatropic reaction.
 3,3-Sigmatropic rearrangements
Sigmatropic rearrangements of order [3,3] are very
common
Generally found in 1,5-hexadiene.

1.Cope rearrangement
2.Aza-Cope rearrangement
3.Clasien rearrangement
 Cope rearrangement:
The thermal rearrangement of 1,5-diene through [3,3] sigmatropic
shift is known as cope rearrangement.
Stereo selectivity in the Cope rearrangement
 Aza-Cope rearrangement
The Aza cope rearrangement is an example of heteroatom version
of cope rearrangement which is [3,3] sigmatropic rearrangement
that shifts single and double bonds between two allylic
components. Aza-Cope rearrangements are generally classified by
the position of the nitrogen in the molecule.
•The transformation of an appropriately substituted
unsaturated iminium ion to an acyl substituted pyrrolidine
by [3,3] sigmatropic rearrangement followed by Mannich
cyclization is an example of aza cope rearrangement (Fig ).
•It is a synthetically powerful reaction, as it is able to create
complex cyclic molecules from simple starting materials.
The Mannich cyclization is irreversible and its product, an
acyl substituted pyrrolidine ring, more stable than that of the
rearrangement.
 Classen rearrangement:
⚫ The simplest example of Claisen rearrangement is the
thermal conversion of allyl vinyl ether in to 4-pentenal

Another example is allyl ethers of phenol. The product of rearrangement is

o- allyl phenol.This reaction proceeds via [3,3] sigmatropic rearrangement.
 (Intramolecular nature of
rearrangemethe
cross over experiments innt)
The intramolecular nature of the rearrangement was firmly established by
which heating of (18) & (19) simultaneously give
the same product as they give separately. There is no information of the
crossover product (22) & (23).
 [5,5] Sigmatropic
Rearrangement
Rearrangement
of 2,4-pentadienylphenyl ethers involves [5,5]
sigmatropic rearrangement. It can be considered a homologous Claisen
rearrangement

The benzidine rearrangement represents another example of a

[5,5] sigmatropic rearrangement