Benzazepine, substituted, rearrangement

Acid catalysed rearrangement of the tetrahydro 1-benzazepine sulfonamides 52 gave the 9-substituted sulfone derivatives 53 plus, in the case of 52b, the 7-substituted isomeric derivative... 

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]. 

A Beckmann rearrangement-reduction sequence has been used to access a number of substituted H- 1-benzazepine derivatives, with the required substituted a-tetralone precursors being prepared by a xanthate-based free radical cyclization process <2006BMC6165>. 

The xanthate transfer process provides a simple and uniquely powerful route to a-tetralones, another family of important aromatic derivatives [69-71]. a-Tetralones are starting materials for the synthesis of a host of medicinally important compoimds. They are precursors to naphthalenes, naphthols, naphthylamines, and ring expansion through the Beckmann rearrangement provides access to benzazepine derivatives. The two examples in Scheme 34 illustrate, on one hand, the possibility of preparing a tetralone with a carbohydrate-derived appendage [69] and, on the other, the synthesis of a substituted naphthol 59 by aromatisation of tetralone 58 through acid... 

The purple charge-transfer complex of indole with tetracyanoethylene decomposes in neutral or basic media to the 3-substituted indole (164), whereas under acidic conditions the 2-(tricyanovinyl)-isoraer is formed. The cyclo-adducts of l-benzyl-3-vinylindole to tetracyanoethylene and maleic anhydride are the cyclobutane (165) and the tetrahydrocarbazole (166), respectivelyThe reaction of 9-methyl-l,2,3,4-tetrahydrocarbazole (167) with dimethyl acetylenedicarboxylate in aqueous acetic acid yields a mixture of the bridged compounds (168) and (169). The photo-adduct (170) of methyl acrylate to 1-benzoylindole rearranges to the benzazepine (171) in hot xylene... 

Rearrangements arising by carbonyl hydrogen abstraction are frequently of value in the synthesis of nitrogen-containing heterocycles. The NN-disubstituted /S-keto-amides (133), on irradiation in benzene, are converted into the 4-hydroxy-2-pyrrolidinones (134), presumably by 8-hydrogen abstraction, in yields of up to 88%.107 Further reports of the cyclization of N-substituted phthalimides have been published. Irradiation of a series of TV-alicyclic phthalimides (135) provides a route to the benzazepines (136) via the cyclobutanols (137) 108 the cw-ring junction in the final product was confirmed by independent synthesis. The... 

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