The Neber Rearrangement

Abstract

An early investigation of the Beckmann rearrangement led Neber to discover that treatment of O ‐sulfonyl ketoximes with base led to the formation of 2 H ‐azirines. Neber's subsequent papers described in detail the full panoply of reactions, intermediates, and byproducts associated with the reaction, including α‐amino ketones formed by acidic hydrolysis of the azirines. This chapter is devoted to the base‐promoted rearrangement of oxime O ‐derivatives, commonly O ‐sulfonates, representing the original “Neber” rearrangement, and the corresponding reaction of N , N , N ‐trimethylhydrazonium iodides, the “modified Neber” rearrangement, discovered by Smith.

Cu(OAc)2-Triggered Cascade Reaction of Malonate-Tethered Acyl Oximes with Indoles, Indole-2-alcohols, and Indole-2-carboxamides

“…Oximes are a class of important organic compounds widely used in Beckmann rearrangement, Semmler–Wolff reaction, and Neber rearrangement owing to the relatively low dissociation energy of the N–O bond. Introducing an acyl group on the oxygen atom avoids the reaction from O–H functionalization and makes the cleavage of N–O bond easier.…”

Structure-Activity Relationships for the Anaesthetic and Analgaesic Properties of Aromatic Ring-Substituted Ketamine Esters

“…While a large number of side-chain analogues are known, relatively few with benzene ring substituents have been reported. The new route that we report here by the Neber rearrangement [16] of readily available substituted 2-phenycyclohexanones gives access to a wide range of benzene-substituted ketamines. We compare two sets of N-alkyl esters as short-acting anaesthetics, exploring Cl, Me, OMe, CF 3 , and OCF 3 benzene ring substituents.…”

“…The use of more nucleophilic precursor reagents (N-methylhydrazine, 4-methoxybenzylamine) was also not successful. We therefore developed a new general route to many of these required norketamines, via the Neber (oxime to α-aminoketone) rearrangement [16] We initially sought to prepare the required new substituted norketamines by the published method for norketamine itself [13] that we had used previously [9], but this was not successful, probably due to the lower nucleophilicity of ammonia compared with methylamine in that process. The use of more nucleophilic precursor reagents (N-methylhydrazine, 4-methoxybenzylamine) was also not successful.…”

“…The use of more nucleophilic precursor reagents (N-methylhydrazine, 4-methoxybenzylamine) was also not successful. We therefore developed a new general route to many of these required norketamines, via the Neber (oxime to α-aminoketone) rearrangement [16] of substituted 2phenycyclohexanones 27a-27p via the hydrazines 28a-28p and hydrazinium salts 29a-29p to give the required norketamines 21, 22 and 30b,c,e-i, k-p (Scheme 2). The known 4-methoxynorketamine analogue 30j could not be prepared by the Neber rearrangement, presumably because of the powerful electron-donating and/or inductive effects of this substituent para to the reaction centre, and was prepared instead by the method described by Sato et al [17].…”

“…The use of more nucleophilic precursor reagents ( N -methylhydrazine, 4-methoxybenzylamine) was also not successful. We therefore developed a new general route to many of these required norketamines, via the Neber (oxime to α-aminoketone) rearrangement [ 16 ] of substituted 2-phenycyclohexanones 27a–27p via the hydrazines 28a–28p and hydrazinium salts 29a – 29p to give the required norketamines 21, 22 and 30b,c , e–i, k–p ( Scheme 2 ).…”