Aldoximes, rearrangement

A nickel catalysed aldoxime rearrangement, to an amide, went out of control after changing the solvent employed. This was found to be due to a slow start and consequent accumulation of unreacted substrate. Changing to a higher operating temperature restored control to the process [3]. 

Catalytic Aldoxime Rearrangement and Coupling into Primaiy, Secondaiy and Tertiary Amides... 

A variety of bifunctional compounds react with the bismaleimides to form polymers by rearrangement reactions. These include amines, sulphides and aldoximes (Figure 18.41). 

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. 

Acyl nitronates (63) derived from primary AN are characterized by two types of such transformations the rearrangement into a-acetoxy aldoximes (219) and elimination of the corresponding carboxylic acids to form nitrile oxides (Scheme 3.63). 

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. 

The formation of a very electrophilic intermediate 258 from 256 and 257 is proposed (equation 78). The hydroxyl group of the oxime adds to 259, giving a reactive cationic species 260 that rearranges and affords the nitrile 261 (in the case of aldoxime, equation 79), or the amide 262 upon hydrolytic workup (equation 80). The conversion of 260 to the nitrilium ion should occur through a concerted [1,2]-intramolecular shift. This procedure can be applied in the conversion of aldoximes to nitriles. It was observed that the stereochemistry of the ketoximes has little effect on the reaction, this fact being explained by the E-Z isomerization of the oxime isomers under the reaction conditions. 

Rearrangement of 273 with simultaneous loss of triphenylphosphine oxide 274 produces the intermediate nitrilium ion 225 that affords the corresponding amide 218. Aldoximes are easily converted to their corresponding nitriles 219 under the same reaction conditions. 

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). 

Generally, the Neber rearrangement is a base-catalysed conversion of 0-acylated ketoximes 523 (but not aldoximes) to a-amino ketones 525 via an isolable 2//-azirine intermediate 524 (equation 232). The azirine itself may be used as a valuable synthetic tooP and the Neber rearrangement is commonly used to produce it. 

Both cyclic and acyclic ketoximes may be used in this transformation and the reaction is usually performed in an alcohol solution containing equimolar quantities of alkoxide. For a successful reaction, the starting material usually contains at least an a-methylene group but the presence of only one a-hydrogen may suffice. When treated with base the 0-acylated aldoximes do not react via the Neber rearrangement and instead they undergo an E2 elimination to cyanides or isocyanides. 

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). 

---