Documente Academic
Documente Profesional
Documente Cultură
By
Bapu R. Thorat
M.Sc. SET. NET. MS-CIT
Assit. Professor
Chemical Reactions
Pericyclic
Reaction
Addition
Elimination
Substitution
Rearrangement
Oxidation
Reduction
Thermal and Photochemical
Electrolysis
Pericyclic Reactions
Free radical
intermediate
Chemical reaction
Mechanism
Charged
intermediate
(Ionic intermediates
such as cation, anion,
zwitter ion, etc)
Transition State
formation
Pericyclic Reactions
Pericyclic Reactions
Thermal Reactions
Activated by heat
Photochemical Reactions
Activated by radiation energy
hv
Ketonic Sensitizer
Cis-
Trans-
Pericyclic Reactions
Pericyclic reactions (pericyclic means shifting of electrons around the circle) are first
explained by the scientist Hoffman and Woodward in 1965.
Pericyclic reactions are highly stereospecific, proceeds through cyclic transition state
(proceed by the simultaneous reorganization of bonding electron pairs by way of cyclic
transition states). The most useful observation of these reactions is the product obtained
during this reactions having different stereochemistry than the reactant.
Electrocyclic
reactionsRing closer and ring
opening
Sigmatropic
rearrangement
Pericyclic
reactions
Cycloaddition
reactions
Ene reactions
Pericyclic Reactions
Electrocyclic reactions-
Process in
which n bonds convert into (n-1) & one
bond and vice versa.
Ring closer-
Molecular orbitals
Antibonding
molecular orbitals
having higher
energy & are
empty at G.S.
CH2
B
A
(Bonding MO)
H2C
CH2
H2C
buta-1,3-diene
C
(Antibonding MO)
Plane of symmetry
C2 axis of symmetry
Anti-Bonding pi-orbital
Bonding pi-orbital
Plane of symmetry
C2 axis of symmetry
Sigma-bond
C2
Orbitals
M
S
A
S
A
C2
A
S
S
A
Orbitals
M
C2
1
S
A
2
A
S
3
S
A
4
A
S
1,3,5-hexatriene, total number of molecular orbitals are six i.e. 1, 2, 3, 3*, 2*, 1* where
1, 2 and 3 are bonding and 3*, 2*and 1* are antibonding molecular orbitals. They are
also denoted as- (1, 2, 3, 4, 5 and 6)
Orbital
M
C2
1
S
A
2
A
S
3
S
A
4
A
S
5
S
A
6
A
S
Node
When we move in molecular orbital, the sign of the orbital change (above the plane or
consider all orbitals below the plane) is called as node.
For a linear conjugated -system the wave function n will posses (n-1) nodes.
If (n-1) is zero or even integer, n will be said to be symmetric with respect to
m and antisymmetric with respect to C2.
If (n-1) is an odd integer n will posses the C2 axis of symmetry and
antisymmetric with respect to m.
Node = 0
Node = 1
Node = 2
Node = 3
CH2
H2C
Z
D
Antibonding MO
Y
C
C2 axis of symmetry
X
B
Bonding MO
W
A
CH2
H2C
Z
D
Antibonding MO
Y
C
C2 axis of symmetry
X
Thermal
HOMO
Bonding MO
W
A
CH2
H2C
Z
D
Antibonding MO
Photochemical
HOMO
Y
C
C2 axis of symmetry
X
B
Bonding MO
W
A
In thermal process the highest occupied molecular orbital [HOMO] is the higher energy
bonding molecular orbital (B in above example).
In photochemical process one electron from higher energy bonding molecular orbital is
excited into low energy antibonding molecular orbital (C in above example) [first
excited state] therefore first excited state containing electron is HOMO (SUMO) i.e.
LUMO lowest unoccupied molecular orbital.
Thermal
Reactions
Photochemical
Reactions
Transition State
Configurational Preference
4n + 2 (aromatic)
Disrotatory
4n (antiaromatic)
Conrotatory
Transition State
Configurational Preference
4n + 2 (aromatic)
Conrotatory
4n (antiaromatic)
Disrotatory
Me
Me
dis,hv
Me
Total Electrons
T.S.
4
Antiaromatic
Symmetry
m
Me
and/or
Process
h
Me
HOMO
3
Node
2
Process allowed
Dis
dis,heat
H H
Me
and/or
H H
Me
Me
Me
Me
H
Me
Process
Total Electrons
T.S.
6
Aromatic
Symmetry
m
HOMO
3
Node
2
Process allowed
Dis
Process
hv
Total Electrons
T.S.
6
Aromatic
Symmetry
C2
HOMO
4
Node
3
Process allowed
Con
hv
3.
HH
Process
h
Me
Me
Dis rotatory
Me
Me
and/or
HH
Me
Me
Total Electrons
T.S.
8
Antiaromatic
Symmetry
m
HOMO
5
Node
4
Process allowed
Dis
Cycloaddition Reactions
It is class of pericyclic reactions in which the system having m electrons is
added into the system having n electrons forming cyclic product.
It is versatile route for the synthesis of cyclic compounds having high degree of
stereo selectivity under thermal and photochemical reaction conditions.
Depending on the number of electrons taking part in the reaction, is called as
(m+n) or (m+n+.) Cycloaddition reactions.
Or
A concerted combination of two -electron systems to form a ring of atoms
having two new bonds and two fewer bonds is called a cycloaddition reaction.
(2+2) cycloaddition
(4+2) cycloaddition
+
O
O
O
NC
CN
+
NC
(4+2) cycloaddition
(2+2+2) cycloaddition
CN
NC
NC
CN
CN
Cycloaddition Reactions
The most common cycloaddition reaction is the [4+2] cyclization known as the
Diels-Alder reaction in which cyclic product is formed from alkene and a diene.
The four -electron system is called as diene and the two -electron system is
called as dienophile.
The stereochemistry of the substituent attached to double bonded carbon atom
is maintained.
The diene containing electron donating group while dienophile containing
electron withdrawing groups are easily undergo (4+2) cycloaddition reaction.
(4+2) cycloaddition
O
(2+2+2) cycloaddition
NC
NC
CN
CN
zwitterions
.
or
diradicals
NC
NC
CN
CN
Cycloaddition Reactions
OAc
COOCH3
OAc
COOCH3
In each case the diene reactant is colored blue, and the new -bonds in the
adduct are colored red. The stereo specificity of these reactions should be
evident.
In the first example, the acetoxy substituents on the diene have identical Econfigurations, and they remain cis to each other in the cyclic adduct.
Likewise, the ester substituents on the dienophile have a trans-configuration
which is maintained in the adduct.
The reactants in the second equation are both monocyclic, so the cycloaddition
adduct has three rings. The orientation of the quinone six - membered ring with
respect to the bicycloheptane system (colored blue) is endo, which means it is
oriented cis to the longest or more unsaturated bridge. This can be explain
by Cis-Principle.
The alternative configuration is called exo.
Cycloaddition Reactions
In cycloaddition reactions, addition of two systems having double bonds takeplace either in same or opposite side of the system. Such mode of addition is very
important to decide the stereo chemistry of product. These different numbers of
modes are named as suprafacial (on the same side) and antrafacial (on the
opposite side).
This specification is usually carried out by keeping a suitable subscript (s or a) after
the number referring to the pi-components. E.g. The Diels-Alder reaction is also
called as (4s+2s) cycloaddition.
[antrafacial]
[suprafcial]
R
+
R
heat
(4s+2s)
R
HOMO
(2s + 2s)
LUMO of unexcited state.
LUMO
(Ground state)
[ , forbidden]
(Excited state)
[ hv, allowed]
(4s + 2s,
(4s + 2s,
, allowed)
, allowed)
HOMO
+
(endo form)
LUMO
HOMO
(exo form)
LUMO
Sigmatropic Rearrangement
Many thermal and photochemical rearrangements are known which involve the
shifting of a -bond flanked by one or more -electron systems to a new
position [i,j] with in the molecule. It is an uncatalyzed intramolecular process.
This rearrangement involve shifting of the -bond, hence called as sigmatropic
rearrangement of the order [i,j]. The i and j are two number set in the square
bracket and the numbering of system is done by starting with atoms from
which the migration of the -bond started.
In some rearrangements, the migrating -bonds lie between two conjugated
bond systems. e.g. Cope & Claisen rearrangements.
e.g. 1.
R1
2'
[1,3] shift
R1
2.
R1
[1,5] shift
R1
3'
(3,3) shift
1'
1
X
2
(X - C<, O)
3
Sigmatropic Rearrangement
Suprafacial and Antrafacial processes
In sigmatropic rearrangement, the -bond migrates across the -bonds through the
two different stereo-chemical sources.
Migrated -bond gets moved across the same face of the conjugated system,
suprafacial process
migrating -bond get reformed on the opposite -electron face of the
conjugated system, antrafacial process i.e. migrating group migrate at opposite
face of the conjugated system.
e.g. [1,5] sigmatropic shift shows both these stereo-chemical consequences as-
H
B
antrafacial
H
B
C
B
C
suprafacial
B
H
Because of these reasons, suprafacial migrations are more common than the
antrafacial shift. As lengthing of the migrating system increases, antrafacial shift
also increases. The antrafacial [1,3] shift is thermally impossible.
Homolytic
..
cleavage
Bond
formation
H
H
H
3
122230 4150
Ground state
Excited state
A similar analysis shows that, for the system [i,j] possess i+j = 4n+2 electrons, the
thermal reaction should be suprafacial and photochemical process should be
antrafacial but for those cases i+j = 4n, the thermal reaction should be antrafacial
and photochemical process should be suprafacial. These rules are summarized as
followi+j
-allowed
h-allowed
4n
antrafacial
suprafacial
4n+2
suprafacial
antrafacial
FMO Methods
Electrocyclic reaction
No. of electrons No. of nodes
involved
4n
Zero or even
Antiaromatic
4n
Odd
Aromatic
Con
4n+2
Zero or even
Aromatic
Dis
4n+2
Odd
Antiaromatic
h-allowed
Dis
Con
Cycloaddition addition
No. of electrons No. of nodes
involved
4n
Zero or even
Antiaromatic
4n
Odd
Aromatic
4n+2
Zero or even
Aromatic
4n+2
Odd
Antiaromatic
Supra-antra
Antra-supra
Supra-supra
Antra-antra
-
h-allowed
Supra-supra
Antra-antra
Supra-antra
Antra-supra
Sigmatropic rearrangement
No. of electrons No. of nodes
involved
Type
of -allowed
transition state
4n
Zero or even
Antiaromatic
4n
Odd
4n+2
4n+2
h-allowed
supra
Aromatic
Antra
Zero or even
Aromatic
supra
Odd
Antiaromatic
antra
Ene Reaction
The joining of a double or triple bond to an alkene reactant having transferable
allylic hydrogen is called an ene reaction.
The allylic hydrogen undergoes 1,5-migration with change in the position of the
allylic double bond.
Like Diels Alder reaction, it is also 6 electron electrocyclic reaction, but here
two sigma-electrons of the allylic C-H -bond takes the place of two -electrons of
the diene in Diels Alder reaction.
+
Y
H
H
X=Y -
Cope Rearrangement
The 1,5-dienes isomerizes {[3,3] rearrangement} on heating up to 3000C. Reaction
is normally reversible and gives mixture of starting material and product. The
position of equilibrium is depends on the stability of the starting material and the
products. The temperature needed for the reaction is depends on the substituents
and relative strain of the double bonds of 1,5-system. If the substituent R is
attached to double bonded carbon then energy of the transition state is lowered and
reaction occurs at 165 1850C.
O
2'
1'
3'
3'
[3,3] rearrangement
HO
1'
2'
3'
[3,3] rearrangement
1'
[3,3] rearrangement
2'
150 0 C,
100%
1hr
3'
OH
[3,3] rearrangement
5.
90%
320 0 C
6.
[3,3] rearrangement
OH
H+
4.
[3,3] rearrangement
2'
1'
98%
H
O
HO
Cope Rearrangement
A common example of Cope rearrangement involving [3,3] sigmatropic
rearrangement in 1,5-diene (meso-3,4-dimethyl-1,5-hexadiene) on heating
(pyrolysis) giving exclusively cis,trans-isomer of 2,6-octadiene. This reaction
proceeds through six membered six electron transition state.
CH3
CH3
H3C
meso-3,4dimethyl-1,5hexadiene
CH3
CH3
CH3
CH3
H3C
Z,E-2,6-octadiene
Bu-n
Bu-n
H3C
CH3
KH, THF, RT
18-crown-6
HO
H3C
H3C
O
CH3
CH3
H3C
CH3
OHC
CH3
CH3
CH3
HO
Bu-n
15 C
KH, THF, RT
18-crown-6
H3C
O
CH3
CH3
H3C
OHC
CH3
CH3
CH3
Claisen Rearrangement
The Claisen rearrangement provides an excellent stereoselective route for the
synthesis of ,-unsaturated carbonyl compounds from allylic alcohols through
allyl vinyl ethers. This reaction involves [3,3]-sigmatropic rearrangement and
takes place through a cyclic six membered transition state. The importance of
this reaction is the formation of carbon-carbon bond due to expense of carbonoxygen bond. It is highly stereoselective leading predominantly E-configuration of
the new double bond. The cyclic transition state preferred chair conformation with
the substituent R1 in the less hindered pseudoequatorial position.
R1
Heat
O
R2
R1
R1
O
R2
O
R2
O
OMe
190 C
decalin
Br
CH3
OH
OMe
OMe
Br
Br
CH3
CH3
Examples
LUMO
HOMO
supra-supra
LUMO
HOMO
antra-antra
LUMO
HOMO
supra-supra
LUMO
HOMO
antra-antra
Examples
2. The intermediate A and the major product B in the following
conversion areCOOH
NaNO2/HCl
NH2
1. A is carbocation and B is
2. A is carbanion and B is
NH2
4. A is benzyne and B is
It is combination of two reactions- Benzyne formation and Diels Alder reaction. The
anthranilic acid undergoes diazotizing followed by decarboxylation forming benzyne. It
shows [4+2] cycloaddition reaction [Diels Alder reaction] forming cyclic product (4).
NaNO2
HNO2
ClH
NaCl
O
COOH
+
COOH
HNO2
NH2
N2 Cl
O
N2 Cl
Examples
3. The structures of the major products X and Y in the following
transformation areO
1.
O
3.
2.
Y=
X=
X=
Y=
O
O
Y=
X=
hv
Y=
4. X =
O
During Diels Alder reaction between cyclic diene and substituted dienophile
forming endo product rather than exo because of favorable secondary force due to
interaction of frontier orbitals of diene and dienophile compounds which leads to lower
the energy of the transition (3). The X further undergoes photochemical [2+2]
cycloaddition reaction of alkene and carbonyl group (Paterno-Buchi reaction) forming
oxetane [four membered cyclic ether].
Examples
O
1,5-carbon
Ans:
1,5-hydrogen
sigmatropic shift
sigmatropic shift
HOMO
HOMO
Process
Total Electrons
6
HOMO
3
Node
2
T.S.
Aromatic
Process allowed
Suprafacial
Examples
LUMO
H
hv
H
A
HOMO
antra-antra
HOMO
supra-supra
Step II is [3+3] sigmatropic rearrangement reaction called Cope rearrangement proceeds through
six membered cyclic (chair form) transition state.
H
A
H
Cyclic chair form six membered
transition state
Example
COOMe
COOMe
O
+
?
COOMe
Step I
HOMO
COOMe
LUMO
COOMe
O
O
or
Step II
COOMe
COOMe
CO2
MeOOC
COOMe
Step III.
or
COOMe
+
COOMe
COOMe
Examples
7. Suggest the mechanism of following reaction.
D
Process
Thermal
Total ele
4
HOMO
2
Node
1
Symmetry
C2
Process allowed
Con
D
D
Examples
8. In the following concerted reaction, the product is formed by a-.
H
1.
2.
3.
4.
Total electrons
6
HOMO
3
Node
2
Symmetry
m
Process allowed
Dis
Process
Thermal
Total electrons
4
HOMO
2
Node
1
Symmetry
C2
Process allowed
Con
H
con rotation
H
H
dis rotation
H
Examples
9. The product formed and the process involved in the following
reaction is OK
OK
[3,3] sigmatropic rearrangement
1.
O
2.
O
3.
O
4.
2
3
1
2
CH2
CH2
CH2
CH2
4
OK
OK
CH2
OK
CH2
CH2
CH2
OK
CH2
CH2
CH2
CH2
H2C
H2C
RT
H3C
H2C
H2C
OCH 3
0 C
97%
+
+
CH2
CH2
H3CO
CH2
CH2
H
O
CH2
CH3
100 C
and
H
H
0 C
0%
0 C
37%
CH2
H2C
CH3
H3C
CH3
CH3
NO 2
80 C
CH2
Bu3SnH
H 3C
PhMe, AIBN
H 3C
H 3C
CH 3
H2C
H2C
RT
H3C
H2C
H2C
CH3
100 C
and
OCH 3
H3CO
H
O
The dienophile containing electron withdrawing group and diene containing electron
donor are undergoes Diels Alder reaction. Along with steric effect, electronic effect
can also plays important role.
O
O
H2C
CH
RT
CH
H2C
CH 2
H3CO
O
CH3
CH3
CH 2
100 C
O
CH2 H3C
CH 2
CH2
OCH 3
O
H3CO
H
O
CH3
O
C
CH 2
H3CO
H
O
H
O
0 C
97%
+
CH2
CH2
CH2
CH2
CH2
H
H
0 C
0%
0 C
37%
CH2
The isolated double bond and diene do not usually take part in intermolecular
Diels Alder reactions, but number of cyclic alkenes ( and alkynes) with
considerable angle strain are reactive dienophiles or dienes. The drawing
force for these reactions is though to be the reduction in angle strain
associated with the transition state for the addition.
H2C
NO 2
H3C
CH3
H 3C
Bu3SnH
80 C
PhMe, AIBN
CH2
H 3C
H 3C
CH3
CH 3
But energy difference between LUMO of dienophile and HOMO of diene is relatively
higher and interaction between them is poor therefore carried out at higher T.
Substituents (bulky substituents) such as methyl group on the diene discourage the diene
from adopting the cisoid conformation and hence hindered the reaction.
-
H2C
CH3
Steric
repulsion
H
H3C
H
H2C
CH3
CH3
CH3
CH3
CH3
H3C
CH3
H3C
CH3
H3C
CH3
CH3
NO 2
N
O
CH2
NO 2
CH2
CH3
H3C
Bu3SnH
80 C
H3C
NO 2
H3C
CH3
+
CH2
CH2
H3C
H3C
NO 2
PhMe, AIBN
H3C
H3C
CH3
H3C
H3C
CH3
Examples
CH3
CH3
a.
i. LDA
iii. H O +
ii.
b.
Et
O
c.
O
i. Et3 N
Cl
H3 C
H
H3 C
O
Cl
d.
ii. PhCH=NPh
Cl
e.
f.
O
g. H3C
CH3
CH3
+
O
MeO
O
h.
CH3
CH3
i.
hv
j.
?
CO2Me
CO2Me
CH3
CH3
3
1
LDA
a.
O
CH3
CH2
H2C
O
CH3
acid
H2C
H3O+
HO
CH3
CH2.
O
CH.
CH3
CH2.
CH3
CH3
CH3
Con rotation
b.
Et
CH3
Et
CH3
CH3
c.
CH3
CH3
Con rotation
CH3
CH3
d . If proceeds through formation of Carbene which shows (2+2) cycloaddition with imine
forming cyclic amide.
OH
H3C
CH3
e.
f.
*
CH2
H3C
CH3
H3C
CH3
H3C
CH3
H3C
CH3
g.
5.
CH3
hv
i.
ii.
CH3
NC
iii.
CN
?
+
NC
CN
CH3
3.
i.
CH3
hv
O
?
ii.
200 0
?
(alkali soluble)
COOCH3
iii.
+
COOCH3