Beckmann Rearrangement 1 Beckmann rearrangement The acidcatalysed conversion

Beckmann Rearrangement 1

Beckmann rearrangement • The acid-catalysed conversion of ketoximes to amides is • • known as the Beckmann rearrangement The Beckmann rearrangement, named after the German chemist Ernst Otto Beckmann (1853– 1923) This rearrangement is occurs in both cyclic and acyclic compounds. Aldoximes are less reactive. Cyclic oximes yield lactams and acyclic oximes yield amides J. Am. Chem. Soc. , 1924, 46 (6), pp 1477– 1483 DOI: 10. 1021/ja 01671 a 018 2

Beckmann rearrangement Reagents: - Conc. H 2 SO 4, HCl, PCl 5, PCl , 3 SOCl , 2 Zn. O, Si. O , 2 PPA (Poly phosphoric acid) etc. , are commonly employed in Beckmann rearrangement. Oxime J. Am. Chem. Soc. , 1924, 46 (6), pp 1477– 1483 DOI: 10. 1021/ja 01671 a 018 Amide 3

Reaction mechanism The first step in the process is formation of an oxime from the aldehyde or ketone, 4

Reaction mechanism This rearrangement take place an alkyl migration with expulsion of the hydroxyl group to form a nitrilium ion followed by hydrolysis. 5

Migratory aptitude • The relative migratory aptitudes of different groups in Beckmann rearrangement is illustrated below. 6

Applications in drug synthesis: • An alternative industrial synthesis method for Paracetamol. It is involves direct acylation of phenol with acetic anhydride catalyzed by HF, conversion of the ketone to a ketoxime with hydroxylamine, followed by the acid-catalyzed Beckmann rearrangement to give the amide Paracetamol 7

Applications in drug synthesis: • The Beckmann rearrangement is also used in the synthesis of 1. DHEA 2. Benazepril 3. Etazepine etc. 8

Applications in polymer synthesis: • Beckmann rearrangement can be rendered catalyticusing cyanuric chloride and zinc chloride as a co-catalyst. For example, cyclododecanonecan be converted to the corresponding lactam, the monomer used in the production of Nylon 12 9

Applications in polymer synthesis: • The Beckmann rearrangement is also used in the synthesis of Nylon 6 10

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