Benzazepines, Beckmann rearrangement

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... 

On the other hand, Evans and Lockhart126 reported that treating 105 (R -R6 = H R7 = OMe R8 = R9 = H) with PPA gave 18 (R1 = H R2 = OMe) as the major product and only some l-benzazepin-2-one. The use of sulfuric acid resulted in tarry products. The 2-tetralone oxime (118, R1 = R2 = R3 = Me R4 = R5 = H) was reported126 to give 24% yield of 86 (R -R4 = Me Rs = R6 = H). Since then, Conley and Lange127 have studied 2-tetralone oximes and shown another mechanism by which the products of Beckmann rearrangement were formed. When the oxime 118 (R1 = Me R2-R6 = H) was treated with phosphorus penta-chloride, a 93-96% yield of the nitrile 119 was obtained. The nitrile could... 

There are two reports in the literature of the Beckmann rearrangement to obtain 3-benzazepin-2-one. The O-tosyl derivative of 118 (R -R6 = H) was heated in methanol at 100° in a sealed tube to give 34 (R -R10 = H) in 78% yield.129 Irradiation of 122 with a high-pressure mercury lamp gave a low yield of 123 via 124.130... 

The Beckmann rearrangement was exploited for the synthesis of a 1-benzazepin-2-one intermediate in the synthesis of oxindole derivatives (14IJPC436). Triflic acid-mediated cyclization of a nitroacetamide yielded a... 

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]. 

---