Beckmann rearrangement reactions

R. E. Gawley, The Beckmann reactions Rearrangements, elimination-additions, fragmentations, and rearrangement-cyclizations , in Organic Reactions, Vol. 35 (Ed. A. S. Kende), Wdey-Intersdence, London, 1988, pp. 1-415. 

R. E. Gawley, The Beckmann Reactions Rearrangements, Elimination-Additions, Fragmentations, and Rearrangement-Cyclizations, Org. React. 1988, 35, 1-420. 

The Beckmann Reactions Rearrangements, Elimination-Additions, Fragmentations, and Rearrangement-Cydizations... 

Another general method for the introduction of a nitrogen atom into a macrocyclic skeleton is via the Beckmann reaction. Rearrangement of cyclotridecanone oxime led to cyclic lactam, which was reduced to amine by lithium aluminium hydride (LAH). Further substitution yielded 14-membered mutuporamine <1999TL5401>. Dieckmann condensation was used for the preparation of 14-membered aza ketone 15 <1999JA2919>, but no experimental details were given. 

Beckmann reactions (rearrangement and rearrangement-cyclization) in synthesis of N-heterocycles 880R(35)1. 

Natural products are derived from plant, marine, and microbial sources and often possess biological activity. They are a source of new drug products each year and continue to play a significant role in the drug discovery and development process. Herein, we will discuss examples of recent natural product synthesis that utilize the previously discussed Beckmann reactions rearrangement, fragmentation, and photo-Beckmann. 

Gawley RE (1988) The Beckmann reactions rearrangement, elimination-additions, fragmentations and rearrangement-cyclizations. Org React 35 14-24... 

Gawley RE (1988) The Beckmann reactions rearrangements, elimination-additions, fragmentations, and rearrangement-cyclizations. In Organic reactions, vol 35. Hoboken, NJ Donaruma LG, Heldt WZ (1960) The Beckmann rearrangement. Org React 11 1-156... 

Reaction of nitromalon-bis-A -methylanilide (105) with sulfuric acid gives A -methylisatin- -oxime (107) and not 4-methylquinoxalin-3-one 1-oxide (108) as originally suggested. This transformation may involve a Beckmann-type rearrangement of the protonated aci-nitro compound (106) prior to dehydrative ring closure. ... 

In addition to the Beckmann reaction, the Schmidt rearrangement is used to generate M-alkylated lactams, too. Alkyl azides 231 react with the cyclic ketones (and aldehydes) in the presence of proton or Lewis acids. On running the inter-molecular reactions, in most cases symmetric ketals 230 have been converted... 

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]. 

Krow and colleagues investigated the migratory preferences of the Schmidt and Beckmann rearrangements in norcamphors. Two isomeric lactams are usually formed in the Schmidt reaction but one lactam is obtained almost exclusively in a Beckmann reaction (equation 178). 

Benzodiazocines 429 were prepared to be tested as calcium-sensitizing agents (equation 181). A mixture of isomeric lactams was obtained when the Schmidt rearrangement was applied to 427, but only one product 428 was produced using the Beckmann reaction. 

Into this group fall the named oxidation rearrangement reactions which proceed with carbon-carbon bond cleavage and 1,2-transfer of an alkyl group to a heteroatom, such as the Baeyer-Villiger reaction (discussed in Chapter 5.1, this volume) and the Beckmann reaction (found in Chapter 5.2, this volume) of ketones, as well as the Hofmann reaction/Schmidt reaction/Curtius reanangement of carboxylic acid derivatives. The two examples discussed here involve related reactions of alcohols. 

Nitrones (268), derived from ketones, undergo a Beckmann-like rearrangement when treated with tosyl chloride in pyridine. Unlike the Beckmann rearrangement, however, the reaction is independent of the nitrone configuration, and shows a preference for vinyl migration. The consequence, for a 4-en-3-one derivative, is the formation of the unusual enamine-lactam (270). The hydroxyl-amino-O-tosylate derivative (269) is considered a likely intermediate (see also Part II, Chap. 2, p. 353). 

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. ... 

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