Transcript Lecture 7 & 8 - Department of Chemistry, IIT Kgp

Lecture 7
Rearrangement Involving Carbocations
R
R
R
TS
Qn: Why is rearrangement quite common to carbocations, and not in case of
radicals or anions?
R
R
R
R
TS
TS
Formation of TS involves combination of bonding orbital (C-R)with the vacant orbital on the carbocation,
singly occupied orbital in case of radical and doubly occupied orbital in case of carbanion.This overlap generates
one bonding and one antibonding scenario.
Antibonding
C
R
Orbital at migrating centre
Bonding
In case of cation, both the electrons occupy the bonding orbital……hence rearrangement is facile
Electron Deficient Carbon
R3C
CR2
Carbocation
Carbene
Carbene
Reactions of Carbocations:
1)
Combination with a nucleophile
2)
Elimination of a proton
3)
Addition to an unsaturated linkage
4)
rearrangement
Y
1) R3C
2) R
3)
C
H2
CH2
-H
RHC
R
R
R
R
R
R
R1
Polymer
R
CH2
R
CH2
R1
R1
R
4)
Y
R3C
R
CH2
R
Product
Pinacol - Pinacolone Rearrangement ---Me
Me
Me
Me
H
Me
Me
Me
HO
O
Me
OH
Pinacolone
Pinacol
Involvs 1, 2 shift of Me :--
Me
Me
Me
Me
HO
OH
H
Me
Me
Me
HO
Me
O
Me
Me
HO
Me
Me
Me
Me
HO
OH2
Me
Me
- H2O
Me
Pinacol
Me
Me
Me
Me
Me
Me
HO
Pinacolone
Qn: Why does the methyl migrate to a tertiary cation?
Ans: To achieve greater stabilization by delocalization of charge
through electron pair of oxygen atom.
Me
For differently substituted pinacols
R2
R1
R1OCC
R3
R3
R4
R1
R2
R3
R4
HO
R1
R2OCC
R2
R4
HO
R4
OH
R1
R1
R3
R2
R2
4 Possibilities
R3
CCOR4
R3
R4
OH
R1
R2
How to decide which will be major?
CCOR3
R4
1)
First decide which carbocation is more stable
2)
Then consider the relative migratory aptitude of the groups
that will undergo 1,2-shift.
Example : -Ph
Me
Ph
Me
Ph
Me
OR
Ph
Me
HO
Ph
OH
Me
O
( Major )
Ph
Me
Me
HO
OH
Ph
Ph
Me
( less stable )
Migratory aptitude aryl>alkyl
usually H>alkyl
Aryl has greater migratory aptitude because it assists in the
departure of leaving group (anchimeric assistance)
Via bridged carbocation
ph
Ph
HO
HO
HO
OH2
Ph
Ph
O
Electron donating groups at the ortho or para position will enhance the migratory aptitude while
electron withdrawing groups will lower the aptitude for migration.
In case of hydride vs alkyl migration
Hydride generally migrates because of the generation of a more
stable carbocation H
H3C
Stabilised by hyperconjugation
H3C
HO
HO
If Methyl migrates
H
Less Stable
HO
CH3
Other ways of carrying out pinacol-pinacolone type rearrangements
H3C
H3C
HO
CH3
H3C
CH3
Ag
Product.
H3C
HO
CH3
Br
CH3
AgBr
H3C
H3C
HO
CH3
HNO2
CH3
NH2
H3C
H3C
HO
CH3
CH3
N2
H3C
CH3
H3C
HO
CH3
Product
Stereochemistry of migration:
The migrating group retains configuration. That means migrating
group is never totally detached
R2
R2 R1
R3
R1
R3
HO
This is also proved by cross over experiments
R'
O
Home Assignment
H
R'
R
R
OH
OH
??
OH
NH2
+
NH2
OH
HNO2
OH
OH
HNO2
??
LECTURE 8
Problems on Pinacol-pinacolone rearrangement
Qn: Write down the Fisher projection formula of the major product
NH2
Me
H
NaNO2
Me
?
HCl
Ph
OH
A
Ans.
Ph
NH2
H
Me
Me
Me
H
Me
Ph
H
Me
Ph
A=
OH
OH
OH
Me
NH2
NH2
HNO2
Ph
Ph
Me
O
Me
H
1
Me
H
Me
2
2
1
Ph
1
OH
Me
H
OH
Me
N2+
Nu (Ph)
Nu
COMe
Me
2
2
Me
2
H
H
Ph
(major product)
Me
N2
2
H
O
Convert
O
OH
OH
OH
O
H
Mg
Benzene
O
OH
4
NH2
2
3
NaNO2
N2
NH2
NaNO2
N2
HCl
5
6
1
HCl
OH
OH
NH2
H
1
3
2
4
4
CHO
2
3
6
( major)
1
OH
OH
O
5
5
OH
OH
OH
(major)
6
Migration to electron deficient Nitrogen
O
O
O
Hofman, Curtius,
Lossen, Schmidt
R
C
R
"a"
C
N
R
A
C
N
Acyl nitrene
N
A
B
B=H
O
"b"
B=
R
C
N
O
R
C
N
R
N
C
O
R
NHCO2H
- CO2
R'OH
RNH2
NHCOOR'
R
Carbamate or Urethane
Hofmann :
O
R
C
O
O
NH2
R
NHBr
RC
C
N
Br
RCON
Lossen :
O
O
R
C
NHOCOR
R
C
N
OCOR
RCON
O
O
R
R
C
N
N
C
N
HN3
HNO2
Curtius
(Schimdt)
RCOOH
RCONHNH2
RCON
H2 O
RCONHOH
Problem
O
R
C
O
NaOBr
NH2
ROCHN
(1/2 eq)
C
NHR
N
Beckman Rearrangement
R1
R2
H2SO4
C
SOCl2
N
P2O5
OH
R1
O
R2
C
BF3
PPA
R2
C
R1
H
NHR1
R2
R2
HO
H2O
N
OH
R2
N
N
OH2
R1
N
R1
O
Anti group always migrates…no question of migratory aptitude!
Mechanism
R2
C
NHR1
N
OH
H
N
OH2
N
Cyclohexanone Oxime
O
[ NH(CH2)5CO]n

NH
Base
Nylon 6
Caprolactam
O
Migration to electron Deficient
Oxygen
O
Peracid
Bayer Villiger Oxidation
R
R
R
OR
or
Peroxide
OH
O
H
R
R
O
R
R1
C
O
O
O
OH
C
OR
R
H
HO
-H
R
R
R
C
O
R
R
O
O
C
O
Rearrangement Involving
Carbanions
X
COOH
Favorskii Rearrangent
1. OH
O
2. H
X
O
OH
R1
Cl
Cl
*
Earlier mechanism
*
O
*
O
*
*
COOH
*
OH
OH
Cl
*
*
However
*
OH
*
COOH +
*
COOH
*
O
*
Cl
*
Cl
*
OH
*
*
*
O
O
O
OH
*
*
*
*
COOH
*
COOH +
O
*
OH
O
O
R1
R3
R4
R2
Application to acyclic systems
H
X
O
R1
OH
R2
R3
R4
R1
R3
R2
X
R4
OH
R1
CO2H
R1
+
R2
CHR3R4
R3
R4
R2
CO2H
OH
OH