SYNTHESIS OF 8-SUBSTITUTED-2,3,4,5-TETRAHYDRO-1H-2-BENZAZEPINES AND 8-SUBSTITUTED-2,3,4,5-TETRAHYDRO-1H-2-BENZAZEPINES

Based on the Schmidt reaction and an iodolactone ring expansion reacti on, two different synthetic routes to substituted 2,3,4,5-tetrahydro-1 H-2-benzazepines were developed. The Schmidt reaction on 2,3-dihydro-2 H-1-naphthalenone (1) gave 3, the product resulting from the alkyl gro up migration, as the major product instead of the tetrazole 2. This pr ompted the investigation of the Schmidt reaction on aromatic ketones 8 and 12. The product 9 due to alkyl group migration was the major prod uct of the Schmidt reaction on 2-methyl-3,4-dihydro-2H-1-naphthalenone (8). The beta-keto diester 12 gave a mixture of decarboxylated lactam s after the Schmidt reaction. In this case, the lactam 13 resulting fr om the migration of the aromatic ring dominated over the other lactam 14. When lactam 14 was subjected to nitration, a single regioisomer wa s produced and transformed to the bromo alcohol 19. The other approach was based on the single pot ring expansion of the iodolactone 22 to t he lactam 23 in the presence of methanolic ammonia. The iodolactone 22 was readily prepared from 2-allylbenzoic acid.