TheBeckmann Reactions: Rearrangements, Elimination–Additions, Fragmentations, and Rearrangement–Cyclizations

Abstract

The Beckmann rearrangement, the acid‐mediated isomerization of oximes to amides, was discovered by Beckmann in 1886. As one of the oldest and most familiar transformations in organic chemistry, it has been reviewed several times. What has become known as the Beckmann fragmentation was in fact first observed by Wallach in 1889 but was not developed extensively until the 1960s. It has been referred to by several names over the years and has also been reviewed. The rearrangement cyclization is the intramolecular cyclization of a nitrilium ion generated by Beckmann rearrangement from an oxime. Within the context of an aromatic terminator, the process was first reported by Goldschmidt in 1895. Wallach reported the first case of an aliphatic terminator in 1901, although the reported structure was incorrect, and Perkin was apparently the first to observe a heteroatom terminator, but he also reported an incorrect structure. The process has been exploited only quite recently. This chapter is an update of these reactions, last reviewed in this series in 1960. Not covered are transformations that have been labeled Beckmann‐type reactions but are mechanistically unrelated. The most prominent of these is the so‐called photochemical Beckmann rearrangement, first observed by De Mayo in 1963 and discussed in a review several years ago. Worthy of mention, however, is the fact that many oximes that suffer fragmentation under acidic conditions undergo rearrangement when photolyzed. Throughout this chapter, the ( E ) and ( Z ) nomenclature is used to describe oxime geometry.

Stereochemical evidence for stabilization of a nitrogen cation by neighboring chlorine or bromine

“…However, a very few apparent exceptions have been documented under certain reaction conditions (8,13). If a syn-migration product is formed, it has been assumed that isomerization of the oxime occurs before rearrangement (6)(7)(8)13). However, such isomerization of the oximes does not occur in the present case.…”

“…It is generally accepted that the Beckmann rearrangement of ketoximes is stereospecific, that N-O bond cleavage occurs with simultaneous migration (e.g., in the cases of O-tosyl (Ts)-phenyl-2-propanone oxime derivatives) (10)(11)(12), and that the relevant C-C bond anti to the leaving group on nitrogen atom migrates (i.e., anti-migration) occurs to maximize antiperiplanar electron delocalization of the C-C σ orbital to the antibonding σ* orbital of the N-O bond (Fig. 2B) (6,7,(10)(11)(12). However, a very few apparent exceptions have been documented under certain reaction conditions (8,13).…”

Nanocatalysts for Rearrangement Reactions

“…128,129 The Beckmann rearrangement generally requires a very high reaction temperature and strong acidic conditions. However, Gai and coworkers have recently revealed that conversion of various ketoximes efficiently takes place under a moderate-temperature regime (130 • C) in the presence of tungstated zirconia solid acid nanocatalysts (5-35 wt% of W).…”

Beckmann Rearrangement of 3-carboxybicyclo[3.3.1]nonane and [3.2.1]octane Oximes

“…Beckmann rearrangement, discovered 130 years ago, has been widely used for the purposes of modern organic synthesis of large variety of natural products, pharmaceuticals and products of bulk industrial processes [1][2][3].…”