Beckmann Rearrangement Reaction mechanism with an application
Rearrangement:- Rearrangement reaction involve a change in carbon skeleton or migration of loops in the molecule. These are organic reactions in which an atom, ion, group of atoms or chemical unit migrates from one carbon atom to another carbon atom in the same or different molecule resulting in a structural isomer of the original molecule. The reaction often includes the breaking and/or making of carbon-carbon sigma bonds.
This rearrangement occurs due to the electron-deficient nitrogen atom.
Principle of Beckmann rearrangement
The acid-catalyzed conversion of keto oxime into N- substituted amide is known as Beckmann Rearrangement.
Beckmann rearrangement is highly stereospecific. Intramolecular and anti-migration may be justified with stereochemistry study. The group which is trans to – OH group migrates hence stereochemical different reactants give a stereochemically different product.
Mechanism Beckmann Rearrangement
Formation of electron-deficient Nitrogen by protonation
Oxime gets protonated in presence of conc. H2SO4 then eliminate water molecule to give positively charged nitrogen species.
The Beckmann rearrangement is often catalyzed by an acid, however other reagents are also reported which promotes the rearrangement. These include tosyl chloride, thionyl chloride, phosphorus pentachloride, phosphorus pentoxide, triethylamine, Zinc chloride, etc.
Step II :-
Migration of alkyl or aryl group.
Alkyl or aryl group which is trans to – OH group migrates to electron-deficient Nitrogen with the formation of Carbonium ion
Nucleophilic attack & Deprotonation.
Water molecule attacks as a nucleophile to carbocation followed by deprotonation. Protonated compound eliminates proton, giving rise to enol form which changes to keto form which is N substituted amide.
The migrating group never detaches itself from the substrate. Thus migration and loss of leaving functionality occur in a synchronous manner.
The rearrangement pattern of the Beckmann reaction depends on many parameters for example structure of migrating
groups. The migrating aptitude does not depend on the nature of the group (as in another rearrangement like pinacol pinacolone) but on its stereochemical arrangement in the oxime. Generally, the group anti-orientation with respect to the leaving group in the oxime molecule migrates. Intramolecular rearrangement always proceeds through bridged-ion.
Beckmann rearrangement is highly stereospecific. Intramolecular and anti-migration may be justified with stereochemistry study. When Beckmann rearrangement is carried out with chiral migrating group then it is found that retention of configuration occurs during the rearrangement.
When a mixture of oximes with a tertiary center next to oxime is subjected to Beckmann rearrangement reaction, cross-over products are obtained showing fragmentation.
The yield of this reaction increases at elevated temperatures and the addition of cocatalyst N-methyl-imidazolium Hydrosulfate.
Cyclic oximes and haloimines yield lactams.
Application of Beckmann Rearrangement :
- Preparation of ɛ-caprolactam- Beckmann Rearrangement is used in the preparation of ɛ-caprolactam which is an important raw material for Nylon -6.
2. Preparation of isoquinoline–
Beckmann Rearrangement is also used in the preparation of isoquinoline. It is an important chemical used in the pharma and specialty chemical industry.
3. Pharmaceutical Sector-
Beckmann Rearrangement is used in the synthesis of paracetamol by converting a ketone to a ketoxime with the help of hydroxylamine
The reaction is also helpful in the synthesis of various steroids and drugs.
4. Other uses
In the production of the chloro bicyclic lactams.
a. Why is the reaction named Beckmann? Who is Beckmann?
Ernst Otto Beckmann (July 4, 1853 – July 12, 1923) was a German pharmacist and chemist who invented this reaction, and hence it is called Beckmann rearrangement.
b. Beckmann rearrangement involves the conversion of what?
Beckmann rearrangement is an acid-catalyzed reaction of ketoximes into N substituted amides.
c. What is oxime?
An oxime is a chemical compound belonging to the imines family, having the general formula as RR’C=NOH, where R is nothing but an organic side-chain and R’ may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime.
d. What are types of rearrangement reactions? What is intramolecular?
Rearrangement reactions are divided into two types, a. Intramolecular, and b. Intermolecular. In intramolecular rearrangement, reaction rearrangement takes place within to group.
e. What is the main difference between Hofmann and Beckmann rearrangement?
The Hofmann rearrangement occurs with an amide whereas the Beckmann rearrangement occurs with N substituted amide.
f. Which types of isomers are formed in rearrangement reactions?
Structural isomers, as products formed have the same molecular formula, but their atoms have different arrangements or bonds.