Name MUHAMMAD ASIF

Roll # 115(222603)
Class B.S Chemistry
Semester 7 th Morning
Session 2018-2022
Topic of Presentation
“Favorskii Rearrangement and its Synthetic
Applications”
Contents
 Introduction

 Characteristics

 Mechanism

 Synthetic Applications
 Introduce by Alexei Yevgrafovich Favorskii
Definition:
The transformation of α-haloketones to esters with rearranged
carbon skeleton
O by the treatment with alkoxide ion.
O
Ph Cl
OCH3
Ph OCH3
O COOH

Cl

NaOH
 Characteristics:
 Electrophilic, carbanion rearrangement or cationotropic rearrangement.
 The product is rearranged carbon skeleton with equal number of ‘C’ atoms.
 Carbon to Carbon migration.
 Halogens are usually Cl-, Br- but not I-.
 Base - Only alkoxide ions give the reaction acting as powerful base; while
other bases like OH–, amines etc. gives carboxylic acids or amides
respectively
When treating material (α-halo ketone ) reacts with alkoxide, it
gives esters.
O
O
Ph Cl
OCH3
Ph OCH3

Ester
 When α-halo ketone reacts with amines, it gives amides.
O

NH
Br
N
O

Amide
 On treating with alkali base, it gives carboxylic acid.
 Cyclic ketones show ring contraction and give the
product correspondence to the reacting material.
O COOH

Cl

NaOH

Carboxylic Acid
with Ring Contraction
 MECHANISM
Deprotonatio • Treating the starting material
n of the with an alkoxide base results
in the ENOLATE formation
ketone
• It leads directly to
Expulsion of
leaving group CYCLOPROPENONE
formation.
Incursion of • It affords TETRAHEDRAL
the INTERMEDIATE that then
Nucleophile fragments.
 Cl Cl
Enolate
Cl

R R' OCH3
R R' R R'

O
O O
Expulsion of Leaving group
Deprotonation
-Cl

R R'
R R'
R R
R' R'
CH3OH
O OCH3 OCH3
COOCH3 C O
O
Tetrahedral Rearrangement
Reprotonation OCH3 (Ring disclosure) Incursion of Nucleophile
 O O
O
Cl Cl
H Cl

OH

Cyclic ketone
O -Cl

C OH O OH O
COOH

NaOH OH
Bond
Nu attack
Cleavage
 Geminal and Vicinal di-haloketones
 Geminal and Vicinal di-haloketones leads to the formation of
α, β-unsaturated esters. In this case, cyclopropenone opening
involves elimination of halide ion
 Br H

HC C C R

Br O H Geminal di-halo ketone

H
H
H2C C C C R
Vicinal di-halo ketone
Br Br O H
 Br H O
Br
HC C CH R C
HC C CH R
OC2H5 -Br
HC CH
Br O
Br O
Br R
Geminal di-halo ketone
C2H5O

O
O O OC2H5
C
R C C C OC2H5 R CH CH C OC2H5
-Br HC CH
H H Br Br R
 Synthetic Applications
1. Amide Formation
2. Ring Contraction in Cyclic system
3. Synthesis of High Strained Carboxylic Acid
1. Amide Formation
NH
Br
N
O

N
Br Br

O O
-Br

N O
O
N

O
O
NH

N
N

Amide
 2. Ring Contraction in Cyclic System
O COOR

Cl

OR

O O
O
Cl Cl
H Cl

OR

-Cl

OR
COOR O O
COOR

Ring ROH
Bond OR
Nu attack
-OR Cleavage
Contraction
3. Synthesis of High Strained Carboxylic Acid
O O

OH

Cl Cl
O

OH

O O O
HOH C
C OH
-OH OH
OH
Carboxylic Acid