Ketoximes Beckmann rearrangement

Keywords ketoximes, Beckmann rearrangement, FeCl3, amides... 

When treated with certain reagents, the ketoximes in particular undergo the Beckmann rearrangement to isomeric acid amides (p. 227). 

The rearrangement of oximes 1 under the influence of acidic reagents to yield A -substituted carboxylic amides 2, is called the Beckmann rearrangement. The reaction is usually applied to ketoximes aldoximes often are less reactive. 

The ketoxime derivatives, required as starting materials, can be prepared from the appropriate aromatic, aliphatic or heterocyclic ketone. Aldoximes (where R is H) do not undergo the rearrangement reaction, but rather an elimination of toluenesulfonic acid to yield a nitrile. With ketoxime tosylates a Beckmann rearrangement may be observed as a side-reaction. 

Beckmann rearrangements of several ketoximes were performed in room-temperature ionic liquids based on l,3-dialkylimida2olium or alkylpyridinium salts containing phosphorus compounds (such as PCI5) by Deng and Peng [59] (Scheme 5.1-31, BP = 1-butylpyridinium). Turnover numbers of up to 6.6 were observed, but the authors did not mention whether the ionic liquid could be reused. 

The reaction that normally occurs on treatment of a ketoxime with a Lewis or proton acid is the Beckmann rearrangement (18-17) fragmentations are considered side reactions, often called abnormal or second-order Beckmann rearrangements. Obviously, the substrates mentioned are much more susceptible to fragmentation than are ordinary ketoximes, since in each case an unshared pair is available to assist in removal of the group cleaving from the carbon. However, fragmentation is a side reaction even with ordinary ketoximes and, in cases where a particularly stable carbocation can be cleaved, may be the main reaction. ... 

A modification of this method, related to the Beckmann rearrangement, entails treatment of a ketoxime with one equivalent of CDI, then four to five equivalents of a reactive halide such as allyl bromide or methyl iodide (R3X) under reflux in acetonitrile for 0.5-1.5 h. Quatemization of the imidazole ring effectively promotes the reaction by increasing the electron-withdrawing effect. The target amides then are obtained by hydrolysis. High yields, neutral conditions, and a very simple procedure make this modification of the synthesis of amides by azolides a very useful alternative. 1243... 

The stereochemical use of the Beckmann rearrangement in assigning configuration to ketoximes has already been referred to, and it also has a large-scale application in the synthesis of the textile polymer Nylon-6 from cyclohexanone oxime (78) via the cyclic amide (lactam, 79) ... 

Conceptually interesting is the synthesis of the oxazole system 94 through a Beckmann rearrangement of a-formyl ketoxime dimethyl acetals 93 which demonstrated the possibility of a non-amino acid pathway in the biosynthesis of marine derived oxazoles <06CC1742>. 

The quest for a solvent-free deprotection procedure has led to the use of relatively benign reagent, ammonium persulfate on silica, for regeneration of carbonyl compounds (Scheme 6.10) [48]. Neat oximes are simply mixed with solid supported reagent and the contents are irradiated in a MW oven to regenerate free aldehydes or ketones in a process that is applicable to both, aldoximes and ketoximes. The critical role of surface needs to be emphasized since the same reagent supported on clay surface delivers predominantly the Beckmann rearrangement products, the amides [49]. 

Rearrangements Emmons found the reagent suitable for Beckmann rearrangements giving water soluble amides. Thus methyl cyclopropyl ketoxime in the medium of 1, 2-dimethoyethane was treated under reflux with stirring with trifluoroacetic anhydride in 1 hr. and refluxed for 1 hr. more. The cyclopropylamine was obtained. 

Several explosions or violent decompositions dining distillation of aldoximes may be attributable to presence of peroxides arising from autoxidation. The peroxides may form on the -C=NOH system (both aldehydes and hydroxylamines perox-idise [1]) or perhaps arise from unreacted aldehyde. Attention has been drawn to an explosion hazard inherent to ketoximes and many of their derivatives (and not limited to them). The hazard is attributed to inadvertent occurence of acidic conditions leading to highly exothermic Beckmann rearrangement reactions accompanied by potentially catastrophic gas evolution. Presence of acidic salts (iron(III)... 

This is the first example of a direct coupling of a diazo compound in a / position of the thiophene nucleus. The Beckmann rearrangement with the ketoxime of 2-thienylketone was found to give poor yields of the aceto-2-thiopheneamide. Furthermore, the Schmidt reaction using hydrazoic and sulphuric acids was investigated and did give rise to aceto-2-thiopheneamide but probably as an eutectic with the isomeric 2-thenoylmethylamide. 

Beckmann rearrangement org chem An intramolecular change of a ketoxime into its isomeric amide when treated with phosphorus pentachloride. bek-man re-g ranj-mont ... 

The rearrangement of ketoximes to amides was discovered more than a century ago, by Beckmann in 1886 , but remains a topic of current interest and stiU retains great synthetic utility. During the last century the Beckmann rearrangement has been frequently reviewedalthough the last major review was almost two decades ago. 

Alternatively, oximes may be converted to O-substituted oximes (typically O-tosyl oximes) making the rearrangement much easier. Sometimes, these oxime derivatives rearrange spontaneously under the condition of their formation and cannot be isolated. Usually, O -tosyl ketoximes rearrange smoothly with exclusive anti migration. Relative to the acid-promoted Beckmann rearrangement, the rearrangement of O -tosyl oximes is much milder and specific. 

Sulfamic acid (+H3NS03 ) has been proved to be an efficient and green catalyst for liquid Beckmann rearrangement of ketoxime in anhydrous acetonitrile. Due to its intrinsic zwitterionic property, the use of a base for the neutralization is avoided and wastes can be reduced. 

Diazotisation of ketoxime carbamates 254 in concentrated sulfuric acid with either isoamyl nitrite or sodium nitrite leads to the Beckmann rearrangement products in moderate to excellent yields with CO2 and N2 as the only by-products " (equation 76). 

The Beckmann rearrangement of ketoximes with triphenylphosphine and iV-chloro-succinimide occurs at room temperature almost instantaneously and their corresponding secondary amides are obtained in high yields (equation 83). The triphenylphosphine 271 is activated by the iV-chlorosuccinimide 270 affording the salt 272, which is attacked by the iV-hydroxy group of the oxime 217 forming the intermediate 273. 

Also, chlorosulfonic acid was demonstrated to be an efficient catalyst in the Beckmann rearrangement of a variety of ketoximes in refluxing toluene, and excellent conversion and selectivity was observed . This procedure can also be applied to the dehydration of aldoximes yielding the corresponding nitriles. 

In the presence of a catalytic amount of an antunony(V) salt (SbCU SbFe ), generated from antimony(V) chloride and silver hexafluoroantimonate, the Beckmann rearrangement of several ketoxime trimethylsilyl ethers proceeds smoothly to give the corresponding amides or lactams in good yields . ... 

Indium trifluoromethanesulfonate was found to be an effective high-yielding catalyst for the facile dehydration of aldoximes to nitriles and Beckmann rearrangement of ketoximes to anilides. ... 

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