Favorskii Rearrangement and its Synthetic Applications

Submitted to: Mam Rukhsana

Submitted by: MUHAMMAD ASIF

Class: B.S. Chemistry

Semester: 7th (Morning)

College Roll # 115

University Roll # 222603

Session: 2018-2022

Course Code: CHM-623

Course Title: Rearrangement and Pericyclic Reactions

Government Graduate College Samanabad Faisalabad

Topic:

Favorskii Rearrangement and its Synthetic Applications

Table of Contents
Sr. # Content Page #
1 Definition 2
2 Characteristics 2
3 Mechanism 2
4 Cyclic Ketones 3
5 Geminal and Vicinal di-haloketones 3
6 Synthetic applications 4
7 Amide formation 4
8 Ring contraction in cyclic system 5
9 Synthesis of high strained carboxylic acid 5
10 References 6

Definition:
1
Favorskii Rearrangement and its Synthetic Applications

The transformation of α-haloketones to esters with rearranged carbon

skeleton by the treatment with alkoxide ions is called Favorskii rearrangement. [1] In
other words it is Base catalyzed rearrangement of an -haloketone to an ester.[2]

 When reacting material treats with alkoxide, it gives esters. [3]

O
O

Ph Cl
OCH3 Ph OCH3

 When it reacts with amines, it gives amides. [4]

O

NH
Br
N
O

 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

[5]

Characteristics: [6]
 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.
Mechanism:
The overall process is quite interesting mechanistically. Typical
conditions consist of treating the starting material with an alkoxide base in a polar
solvent, but there are many options available. A possible mechanism for the process
is shown below. Deprotonation of the ketone results in the enolate. This can either
lead directly to cyclopropenone by expulsion of the leaving group or proceed initially
to an ox allylic cation, which then undergoes dis-rotatory ring closure to the
cyclopropenone. Nucleophilic attack on the cyclopropenone affords a tetrahedral

2
Favorskii Rearrangement and its Synthetic Applications

intermediate that then fragments. A carbanion often written as an intervening

species; this is protonated to give the product(s). [7]

Cl
Cl Cl

R R' OCH3
R R' R R'

O O O

R R'
R R'
R R
R' R'
CH3OH
O OCH3 OCH3
COOCH3 COOCH3
O

In Cyclic ketones, alkali base (or alkoxide) attacks on the α-carbon and deprotonates
it. Then halogen group leaves which results in cyclopropenone ring. When this ring
open, this results in ring contraction. [8]
O O
O
Cl Cl
H Cl

OH

O -Cl

C OH O OH O
COOH

NaOH OH
Bond
Nu attack
-ONa Cleavage

Geminal and Vicinal di-haloketones leads to the formation of α, β-unsaturated

esters. In this case, cyclopropenone opening involves elimination of halide ion. [9]

3
Favorskii Rearrangement and its Synthetic Applications

Br H O
Br
HC C CH R C
HC C CH R
OC2H5 -Br
HC CH
Br O
Br O
Br R
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: [10]
The α-halo ketone will arrange to Amide when reacts with amine.

NH
Br
N
O

4
Favorskii Rearrangement and its Synthetic Applications

NH
Br Br

O O
-Br

N O
O
N

O
O
NH

N
N

2. Ring Contraction in Cyclic System:[11]

The important synthetic application of favorskii rearrangement is that it is used for
ring contraction in cyclic system.

O COOR

Cl

OR

5
Favorskii Rearrangement and its Synthetic Applications

O O
O
Cl Cl
H Cl

OR

-Cl

OR
COOR O O
COOR

ROH OR
Bond
Nu attack
-OR Cleavage

3. Synthesis of High Strained Carboxylic Acid: [12]

It is used for the synthesis of high strained carboxylic acid. An interesting example is
the conversion of cyclobutyl into cyclopropyl system.

O O

OH

Cl Cl
O

OH

O O O
HOH C
C OH
-OH OH
OH

References:
[1]- Rearrangement and Pericyclic Reactions by Dr. Muhammad Shoaib.
[2]- Reaction Mechanisms and Pericyclic Reactions by Prof. Ashok Sharma.
[3]- Rearrangement and Pericyclic Reactions by Dr. Muhammad Shoaib.
[4]- Rearrangement and Pericyclic Reactions by Dr. Muhammad Shoaib.
[5]- Advanced Organic Chemistry Reactions and Mechanisms by Maya Shankar Singh.
[6]- Reaction Mechanisms and Pericyclic Reactions by Prof. Ashok Sharma.

6
Favorskii Rearrangement and its Synthetic Applications

[7]- Molecular Rearrangement in Organic Synthesis by Wiley, Edited by Christian M.

Rojas
[8]- Mam Rukhsana Notes.
[9]- Organic Chemistry for Graduate Students by Haq Nawaz Bhatti.
[10]- Rearrangement and Pericyclic Reactions by Dr. Muhammad Shoaib.
[11]- Reaction Mechanisms and Pericyclic Reactions by Prof. Ashok Sharma.
[12]- Molecular Rearrangement in Organic Synthesis by Wiley, Edited by Christian M.
Rojas