Applications Beckmann rearrangement

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) ... 

A 10-carbon oxime at 60°C was stored in an insulated container, and within 24 h the temperature had risen to 125°C, possibly owing to an exothermic Beckmann rearrangement to an amide. Application of cooling prevented a thermal runaway. 

Zeolites have also been described as efficient catalysts for acylation,11 for the preparation of acetals,12 and proved to be useful for acetal hydrolysis13 or intramolecular lactonization of hydroxyalkanoic acids,14 to name a few examples of their application. A number of isomerizations and skeletal rearrangements promoted by these porous materials have also been reported. From these, we can underline two important industrial processes such as the isomerization of xylenes,2 and the Beckmann rearrangement of cyclohexanone oxime to e-caprolactam,15 which is an intermediate for polyamide manufacture. Other applications include the conversion of n-butane to isobutane,16 Fries rearrangement of phenyl esters,17 or the rearrangement of epoxides to carbonyl compounds.18... 

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]. 

Perhaps the most notable application of the Beckmann rearrangement is in the industrial production of 8-caprolactam from cyclohexanone (or its oxime), which is used as monomer for the polymerization to a polyamide for the production of synthetic fibres (for example, nylon 6). Furthermore, Beckmann rearrangement provides a facile route for the... 

The previous referred inconveniences have prompted an increasing interest in the development of alternative, essentially neutral and more environmental-friendly catalysts to promote the rearrangement of O-unsubstituted oximes. The development of highly efficient and selective transformations and also of processes for catalyst recovery and its reuse are the aim of some of the more recent studies. Much of this work is being done in industry to improve current production processes and is the subject of new patent applications. During the last two decades environment concerns have led to the development of green, simple and cost-effective catalytic systems for the Beckmann rearrangement. 

Zeolites and other mesoporous materials are excellent catalysts for industrial and laboratory applications. Favourable characteristics are their capacity to immobihze homogenous catalysts rendering them heterogeneous, their thermal stability, and the ease of separation from the reaction products and reuse in hquid- and gas-phase conditions. The pore size and Brpnsted and Lewis acidic properties are determinant for their use as catalyst in the Beckmann rearrangement. Recently, a review on the use of zeolites and mesoporous materials in the Beckmann rearrangement was published. ... 

The same strategy had application in several other heterocyclic compounds, to obtain either amine or carboxylic acid derivatives. A process for the production of 4-amino-5-methylpyrazole derivative 325 using the Beckmann rearrangement as a key step was the subject of a new patent ° (equation 119). 

Similarly, the application of Tamura s Beckmann rearrangement reagent to ketones 367 and 370 afforded the appropriate lactams 368 and 371 to be cyclized to the indolizidine nucleus 369 and yilP (equations 146 and 147). 

Although the Beckmann fragmentation may be regarded as a limitation for the application of the Beckmann rearrangement, it provides a synthetic method to produce nitrile compounds. Some examples from the recent literature are collected in the next section. 

The production of the nylon precursor e-caprolactam via the Beckmann rearrangement is one of the largest industrial processes worldwide. There are a large number of synthetic routes to e-caprolactam, most of which need to be improved because, without exception, all are multistage processes that produce large amounts of by-products, primarily ammonium sulfate. Due to its industrial application, the improvement of the Beckmann rearrangement of e-caprolactam was the aim of several smdies and a lot of scientific papers, patents and book chapters have been published on this topic during the last century. 

Benzoxazoles.1 Benzoxazoles (2) are obtained in generally good yield by Beckmann rearrangement of the oxime of 2 -hydroxyacetophenones (1) using POCl3-DMA in CH3CN at 30° (equation I). The method is applicable to synthesis of hydroxy-substituted benzoxazoles, which are usually difficult to prepare. 

A serious shortcoming of TS-1, in the context of fine chemicals manufacture, is the restriction to substrates that can be accommodated in the relatively small (5.lx5.5 A2) pores of this molecular sieve, e.g. cyclohexene is not epoxidised. This is not the case, however, with ketone ammoximation which involves in situ formation of hydroxylamine by titanium-catalysed oxidation of NH3 with H202. The NH2OH then reacts with the ketone in the bulk solution, which means that the reaction is, in principle, applicable to any ketone (or aldehyde). Indeed it was applied to the synthesis of the oxime of p-hydroxyacetophenone, which is converted, via Beckmann rearrangement, to the analgesic, paracetamol (Fig. 1.24) [75]. 

This is a good step because it is the normal Beckmann rearrangement. However, to get from this intermediate to the open-chain product took a fairly large number of creative steps. Application of Occam s razor suggests that the initial fragmentation occurs early in the mechanism. 

Lee, J. K., Kim, D.-C., Song, C. E., Lee, S.-g. Thermal behaviors of ionic liquids under microwave irradiation and their application on microwave-assisted catalytic Beckmann rearrangement of ketoximes. Synth. Commun. 2003, 33, 2301-2307. 

Butler, R. N., O Donoghue, D. A. Direct detection of intermediates and synthetic applications of the reaction of thionyl chloride with oximes of substituted acetophenones and benzaldehydes Beckmann rearrangements. J. Chem. Res., Synop. 1983,18-19. 

The Beckmann rearrangement of oximes to give the corresponding amides (equation 93) is well known and was reviewed in detail328,335. The reaction is usually carried out in the presence of strong acids, although modifications were developed which use much milder conditions, e.g. by application of benzenesulfonyl chloride in alkaline... 

The A-Boc group is rapidly removed on reaction with AlClj under microwave irradiation. Friedel-Crafts reactions. Both alkylation and acylation of arenes can be performed without solvent, by thoroughly grinding the reagents in an agate mortar and pestle at room temperature. (This technique is also applicable to Beckmann rearrangement of oximes in nearly quantitative yields. )... 

Beckmann rearrangement to ethyl 5-cyano-2-oximinovalerate. Hydrogenation over Raney nickel and a basic co-catalyst and hydrolysis afforded DL-lysine monohydrochloride in 63% overall yield from cyclohexanone. A less fully studied application of the sequence to cyclopentanone affords DL-ornithine in overall yield of 21%. W. H. Hartung and F. Crossley, Org. Syn., Coll. Vol.,2.363 (1943)... 

It is known that nitrilium salts can be prepared by alkylation of nitriles , via the reaction of imidoyl chlorides with Lewis acids as well as by Beckmann rearrangement of oximes . The application of nitrilium salts in organic synthesis is summarized in a number of reviews " . In this connection it is appropriate to mention another three-component one-pot synthesis of 5,6-dihydro-4. -l,3-oxazines 40 based on the reaction of aldehydes with iV-tcr/-butylnitrilium salt 41 which, however, proceeds without the participation of Af-acyliminium ions . The reaction is carried out by mixing the aliphatic or aromatic aldehyde, tcrt-butyl chloride and Lewis acid (SbCljjSnC ) in benzonitrile solution (equations 16 and 17). 

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