Beckmann reaction conditions

Substituents R, R at the starting oxime 1 can be H, alkyl, or aryl. The reaction conditions for the Beckmann rearrangement often are quite drastic (e.g. concentrated sulfuric acid at 120 °C), which generally limits the scope to less sensitive substrates. The required oxime can be easily prepared from the respective aldehyde or ketone and hydroxylamine. 

The most widely used route to l-benzazepin-2-ones involves the Beckmann or Schmidt reaction of the easily accessible 1-tetralones. Many biologically active compounds described in this review have been prepared on the basis of these reactions they have been fully reviewed [2], In the Beckmann reaction of 1-tetralone oximes, polyphosphoric acid is used as a catalyst-solvent in most instances. Aryl migration generally takes precedence over alkyl migration under these reaction conditions, and various 1-tetralone oximes substituted on the aromatic and/or aliphatic rings can be converted to the appropriate 2,3,4,5-tetrahydro-l//-l-benzazepin-2-ones (51) [5, 20-23, 36, 59, 65, 80, 107-112]. Both courses of the rearrangement occur in some instances, yielding l-benzazepin-2-ones (51) and the isomeric 2-benzazepine-l-ones, probably due to electronic effects of the substituents [90, 113, 114]. 

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. 

Several different reaction conditions were tested to perform the Beckmann rearrangement of the substituted thiophene 323 (equation 118). The reaction of the tosyl oxime derivative was found to be the best available method, and 324 was obtained in high yield °. ... 

The Beckmann fragmentation may compete seriously with the Beckmann rearrangement. Both reactions may proceed via common intermediates and the observed selectivity strongly depends on the structural features of the starting compound. Reaction conditions can also have a strong influence on the success of the reaction. 

Although both the Beckmann and Neber reactions can use oxime derivatives as starting materials, O-unsubstituted oximes cannot undergo the Neber rearrangement. The latter occurs only in strongly alkaline reaction conditions while the former can also proceed in both acid and basic media. As a consequence, the Neber rearrangement will only be a possible side reaction of base-induced Beckmann rearrangements. 

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. 

Activation of the oxime with benzenesulfonyl chloride or p-toluenesulfonyl chloride leads to sulfonate esters which undergo the Beckmann reaction with or without isolation. - The sulfonate esters also rearrange under mild reaction conditions on silica gel.i Under neutral conditions, lV,A(-carbonyldiimida-zole activates oximes in the presence of allyl bromide, followed by spontaneous Beckmann rearrangement. ... 

An unexpected reductive rearrangement was observed in the reaction of the dioxime (33) with diisobutylaluminum hydride in dichloromethane, leading to the diamine (34 equation 21). It should be noted that attempted reaction of (33) under various Beckmann rearrangement conditions resulted either in extensive decomposition or fragmentation. 

Reaction of ketones with hydrazoic acid proceeds similarly to the Beckmann rearrangement to give amides, while aldehydes yield nitriles and formamides under analogous reaction conditions (equations 4 and 5). 

Although many solid-acid catalysts have been reported for the vapor-phase Beckmann rearrangement [2], their performance has been less than satisfactory from an industrial standpoint and the heterogeneously catalyzed Beckmann rearrangement has not yet been commercialized. In this chapter heterogeneous catalysis of the Beckmann rearrangement, its mechanism, and acid properties and reaction conditions suitable for the reaction will be reviewed. 

Beckmann Rearrangement. The Beckmann rearrangement of cyclohexanone oxime to s-caprolactam (Scheme 8.15) is an important step in the synthesis of s-caprolactam, the monomer for nylon-6. Traditional reaction conditions involve the use of sulfuric acid as a catalyst for this conversion, and require... 

When the Beckmann reaction was performed with mesylated oxime intermediate 113, lactam 112, from the Beckmann rearrangement, was obtained as the sole product tScheme 5.261. thus shutting down the Beckmann fragmentation pathway.This reaction is similar to what White and coworkers observed during their morphine synthesis. Beckmann reaction of an intermediate brosylated oxime in acetic acid provided the desired lactam, whereas the reaction of the corresponding oxime under acidic conditions did not yield any lactam... 

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