POLONOVSKY N-Oxide Rearrangement

POLONOVSKY N-oxide Rearrangement Conversion of heterocyclic N-oxIdes to a-acetoxyheterocycles... 

This is an example of the Polonovsky N-oxide rearrangement (1) which was previously used to prepare 3-hydroxy-l,4-benzodiazepine-2-ones (2). 

POLONOVSKY N Oxide rearrangement 302 POMERANZ FRITSCH SCHLITTER MULLER Isoquinoline synthesis 303 Ponndort 251... 

It will perhaps be recalled from the earlier volume that such N-oxides are prone to undergo the Polonovski rearrangement when treated with acetic anhydride, and that this was illustrated by the formation of oxazepam. It is not surprising that the N-methyl analogue (4) also undergoes this process, and hydrolysis of the resulting acetate gives... 

The chemical conversion of alkaloids of the vobasine type into those of the ervatamine type can readily be effected, using a modified Polonovski reaction. This involves formation of an N-oxide and its rearrangement, using trifluoroacetic anhydride as reagent. Dregamine (65) has been converted into 20-epi-ervatamine... 

A simple and efficient procedure for the direct oxidation of C-3 of l,4-benzodiazepin-2-ones, applicable to the preparation of the anxiolytic agents oxazepam and lorazepam, has been developed that represents an improvement over the well-established Polonovsky rearrangement of the N-4 oxide <20060PD1192>. Iodine in AcOH at 65 °C catalyzed acetoxylation in a reaction that involved iodination at C-3 followed by a rapid nucleophilic displacement by KOAc. The liberated HI was recycled to iodine by inclusion of a stoichiometric oxidant, with K2S2O8 being the optimal compromise of cost, availability, and efficiency. 

Scheme 10.9. A representation of the Polonovski reaction in which the A-oxide of A-methyl-A-phenylaniline is treated with ethanoic anhydride (acetic anhydride) and rearrangement occurs with migration of oxygen from N C and formation of the acetate ester of N,N-diphentylaminomethanol. The aminoester, on hydrolysis, produces acetate, methanal (formaldehyde) and iV-phenylaniline. See Lounasmaa, M. Koskinen, A. Heterocycles, 1984,22,1591 and Grierson, D. The Polonovski Reaction, in Paquette, L. A. (ed.). Organic Reactions, Vol. 39, Wiley, Hoboken, NJ, 1990.

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