Aldoximes Beckmann rearrangement

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. 

With aldoximes (R = H) a migration of hydrogen is seldom found. The Beckmann rearrangement therefore does not give access to iV-unsubstituted amides. 

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. 

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]. 

A simple montmorillonite K 10 clay surface is one among numerous acidic supports that have been explored for the Beckmann rearrangement of oximes (Scheme 6.27) [54]. However, the conditions are not adaptable for the aldoximes that are readily dehydrated to the corresponding nitriles under solventless conditions. Zinc chloride has been used in the above rearrangement for benzaldehyde and 2-hydroxyacetophe-none, the later being adapted for the synthesis of benzoxazoles. 

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)... 

Rare-earth exchanged [Ce ", La ", Sm"" and RE (RE = La/Ce/Pr/Nd)] Na-Y zeolites, K-10 montmorillonite clay and amorphous silica-alumina have also been employed as solid acid catalysts for the vapour-phase Beckmann rearrangement of salicylaldoxime 245 to benzoxazole 248 (equation 74) and of cinnamaldoxime to isoquinoline . Under appropriate reaction conditions on zeolites, salicyl aldoxime 245 undergoes E-Z isomerization followed by Beckmann rearrangement and leads to the formation of benzoxazole 248 as the major product. Fragmentation product 247 and primary amide 246 are formed as minor compounds. When catalysts with both Br0nsted and Lewis acidity were used, a correlation between the amount of Br0nsted acid sites and benzoxazole 248 yields was observed. 

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. 

The same activity is presented by an iridium complex [Ir(Cp )Cl2]2 that catalyses the Beckmann rearrangement of aromatic, aliphatic and heteroaromatic aldoximes 276 into the corresponding primary amide 277 in good to excellent yields (78-97%) (equation 85). 

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. ... 

Under solvent-free conditions, one-step Beckmann rearrangement of a variety of ketones and aldehydes proceeded in the presence of alumina sulfuric acid 285 (equation 93). Good selectivities were also obtained in the rearrangement of aldoximes to primary amides using zinc oxide as catalyst " (equation 93). 

Synthetically speaking, the Beckmann rearrangement of an aldoxime E or Z) wiU produce a primary amide (equation 99). 

Hoffenberg, D. S., Hauser, C. R. Dehydration or Beckmann rearrangement of aldoximes with boron... 

Nitriles may be prepared by dehydration of aldoximes an attempt to effect a Beckmann rearrangement on the oxime (481) of 5-methoxy-4-oxopyran-2-carboxaldehyde gives the nitrile (482) but under milder conditions only the chloride (483) and the chloronitrile (484) are obtained (75JHC219). 

The acid-catalyzed conversion of ketoximes and aldoximes to amides or amines (the amide is often hydrolyzed to the corresponding amine under the reaction conditions) is known as the Beckmann rearrangement after its discoverer.147 The reaction and its widely accepted mechanism are shown in Equation 6.54. 

When the reaction is carried out in boiling DMSO, no significant gain in the yield of benzamide (30%) is observed. Since under these conditions the primary dehydration of aldoximes is evident, the formation of benzamide is most likely to result from hydration of the intermediate benzonitrile rather than by the Beckmann rearrangement scheme. 

The fact that under the same conditions acetophenone oxime does not form amides, but remains intact, also provides evidence against the classical Beckmann rearrangement. The conditions found can be employed for preparing amides from nitriles and aldoximes, especially when the latter contain fragments unstable to acids. In the absence of DMSO, benzaldoxime is dehydrated with alkali only at the boiling point (200°C). 

Keywords aldoxime, p-toluenesulfonyl chloride, pyridine, alumina, Beckmann rearrangement, microwave irradiation, nitrile... 

Under the relatively mild conditions of chlorosulfonic acid in toluene, ketoximes undergo Beckmann rearrangement, whereas aldoximes dehydrate to nitriles.90... 

The first photochemical Beckmann rearrangement of aromatic aldoximes was reported in 1963. Subsequently, cyclohexanone oxime was shown to rearrange, upon photolysis, to caprolactam. Although the presence of oxaziridines in the solutions of photolyzed oximes was demonstrated, no oxaziridines have been isolated from these reaction mixtures presumably because of the general instability of oxaziridines that have no substituents on the ring nitrogen. The qualitative results are consistent with the intermediacy of oxaziridines in the photolysis of oximes to amides, yet the possibility of the reactions following other pathways cannot be ruled out. ... 

Rearrangements. Horning and Stromberg found PPA an excellent solvent-reagent for effecting Beckmann rearrangement of ketoximes°° and aldoximes.° For example, benzophenone oxime (2 g.) when stirred manually with PPA (60 g.) at 130° dissolved in about 10 min., and after dilution of the clear solution with water... 

InCls can be used as an efficient reagent for the conversion of aldoximes to nitriles and ketoximes to amides. Benzaldoxime gives benzonitrile, and benzophenone oxime is converted to the Beckmann rearrangement product, benzanilide, in 95% yield (Scheme 8.135) [179]. Sonication of a mixture of a carbonyl compound, an amine, and diethyl phosphite in fhe presence of a catalytic amount of InCls produces a-aminophosphonate (Scheme 8.136) [180]. 

Oximes are formed as intermediates in this reduction74 and this may be the reason why secondary amines can also be obtained. In an acid medium oximes may be hydrolysed to carbonyl compounds, and aldoximes may undergo the Beckmann rearrangement,... 

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